Exemple #1
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def test_sanity():
    """Test to build variant dicts"""

    vcf = get_vcf_file()

    head = get_header(vcf)

    header_line = head.header

    for line in vcf:
        if not line.startswith('#'):
            variant = get_variant_dict(variant_line=line,
                                       header_line=header_line)
def test_sanity():
    """Test to build variant dicts"""
    
    vcf = get_vcf_file()
    
    head = get_header(vcf)
    
    header_line = head.header
    
    for line in vcf:
        if not line.startswith('#'):
            variant = get_variant_dict(
                variant_line = line, 
                header_line = header_line
            )
Exemple #3
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def test_wrong_variant():
    """Test to build a variant dict with a wrong formatted variant"""

    vcf = get_vcf_file()

    head = get_header(vcf)

    header_line = head.header

    # Missing one gt call
    wrong_variant = '3\t973348\t.\tG\tA\t100\tPASS\tMQ=1\tGT:GQ\t0/0:60\t0/0:60\n'

    with pytest.raises(SyntaxError):
        variant = get_variant_dict(variant_line=wrong_variant,
                                   header_line=header_line)
def test_wrong_variant():
    """Test to build a variant dict with a wrong formatted variant"""
    
    vcf = get_vcf_file()
    
    head = get_header(vcf)
    
    header_line = head.header
    
    # Missing one gt call
    wrong_variant = '3\t973348\t.\tG\tA\t100\tPASS\tMQ=1\tGT:GQ\t0/0:60\t0/0:60\n'
    
    with pytest.raises(SyntaxError):
        variant = get_variant_dict(
            variant_line = wrong_variant, 
            header_line = header_line
        )
Exemple #5
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    def _formated_variants(self, raw_variants, case_obj):
        """Return variant objects

            Args:
                raw_variants (Iterable): An iterable with variant lines
                case_obj (puzzle.nodels.Case): A case object

        """
        vcf_file_path = case_obj.variant_source

        logger.info("Parsing file {0}".format(vcf_file_path))
        head = HeaderParser()
        handle = get_vcf_handle(infile=vcf_file_path)
        # Parse the header
        for line in handle:
            line = line.rstrip()
            if line.startswith("#"):
                if line.startswith("##"):
                    head.parse_meta_data(line)
                else:
                    head.parse_header_line(line)
            else:
                break

        handle.close()

        header_line = head.header

        # Get the individual ids for individuals in vcf file
        vcf_individuals = set([ind_id for ind_id in head.individuals])

        variant_columns = ["CHROM", "POS", "ID", "REF", "ALT", "QUAL", "FILTER"]

        vep_header = head.vep_columns
        snpeff_header = head.snpeff_columns

        index = 0
        for variant_line in raw_variants:
            if not variant_line.startswith("#"):
                index += 1
                # Create a variant dict:
                variant_dict = get_variant_dict(variant_line=variant_line, header_line=header_line)
                variant_dict["CHROM"] = variant_dict["CHROM"].lstrip("chrCHR")
                # Crreate a info dict:
                info_dict = get_info_dict(info_line=variant_dict["INFO"])
                # Check if vep annotation:
                vep_string = info_dict.get("CSQ")

                # Check if snpeff annotation:
                snpeff_string = info_dict.get("ANN")

                if vep_string:
                    # Get the vep annotations
                    vep_info = get_vep_info(vep_string=vep_string, vep_header=vep_header)

                elif snpeff_string:
                    # Get the vep annotations
                    snpeff_info = get_snpeff_info(snpeff_string=snpeff_string, snpeff_header=snpeff_header)

                variant = Variant(**{column: variant_dict.get(column, ".") for column in variant_columns})

                logger.debug("Creating a variant object of variant {0}".format(variant.get("variant_id")))

                variant["index"] = index
                logger.debug("Updating index to: {0}".format(index))

                variant["start"] = int(variant_dict["POS"])

                if self.variant_type == "sv":
                    other_chrom = variant["CHROM"]
                    # If we have a translocation:
                    if ":" in variant_dict["ALT"] and not "<" in variant_dict["ALT"]:
                        other_coordinates = variant_dict["ALT"].strip("ACGTN[]").split(":")
                        other_chrom = other_coordinates[0].lstrip("chrCHR")
                        other_position = other_coordinates[1]
                        variant["stop"] = other_position

                        # Set 'infinity' to length if translocation
                        variant["sv_len"] = float("inf")
                    else:
                        variant["stop"] = int(info_dict.get("END", variant_dict["POS"]))
                        variant["sv_len"] = variant["stop"] - variant["start"]

                    variant["stop_chrom"] = other_chrom

                else:
                    variant["stop"] = int(variant_dict["POS"]) + (len(variant_dict["REF"]) - len(variant_dict["ALT"]))

                variant["sv_type"] = info_dict.get("SVTYPE")
                variant["cytoband_start"] = get_cytoband_coord(chrom=variant["CHROM"], pos=variant["start"])
                if variant.get("stop_chrom"):
                    variant["cytoband_stop"] = get_cytoband_coord(chrom=variant["stop_chrom"], pos=variant["stop"])

                # It would be easy to update these keys...
                thousand_g = info_dict.get("1000GAF")
                if thousand_g:
                    logger.debug("Updating thousand_g to: {0}".format(thousand_g))
                    variant["thousand_g"] = float(thousand_g)
                    variant.add_frequency("1000GAF", variant.get("thousand_g"))

                # SV specific tag for number of occurances
                occurances = info_dict.get("OCC")
                if occurances:
                    logger.debug("Updating occurances to: {0}".format(occurances))
                    variant["occurances"] = float(occurances)
                    variant.add_frequency("OCC", occurances)

                cadd_score = info_dict.get("CADD")
                if cadd_score:
                    logger.debug("Updating cadd_score to: {0}".format(cadd_score))
                    variant["cadd_score"] = float(cadd_score)

                rank_score_entry = info_dict.get("RankScore")
                if rank_score_entry:
                    for family_annotation in rank_score_entry.split(","):
                        rank_score = family_annotation.split(":")[-1]
                    logger.debug("Updating rank_score to: {0}".format(rank_score))
                    variant["rank_score"] = float(rank_score)

                genetic_models_entry = info_dict.get("GeneticModels")
                if genetic_models_entry:
                    genetic_models = []
                    for family_annotation in genetic_models_entry.split(","):
                        for genetic_model in family_annotation.split(":")[-1].split("|"):
                            genetic_models.append(genetic_model)
                    logger.debug("Updating rank_score to: {0}".format(rank_score))
                    variant["genetic_models"] = genetic_models

                # Add genotype calls:
                for individual in case_obj.individuals:
                    sample_id = individual.ind_id

                    if sample_id in vcf_individuals:

                        raw_call = dict(zip(variant_dict["FORMAT"].split(":"), variant_dict[sample_id].split(":")))
                        variant.add_individual(
                            Genotype(
                                sample_id=sample_id,
                                genotype=raw_call.get("GT", "./."),
                                case_id=individual.case_name,
                                phenotype=individual.phenotype,
                                ref_depth=raw_call.get("AD", ",").split(",")[0],
                                alt_depth=raw_call.get("AD", ",").split(",")[1],
                                genotype_quality=raw_call.get("GQ", "."),
                                depth=raw_call.get("DP", "."),
                                supporting_evidence=raw_call.get("SU", "0"),
                                pe_support=raw_call.get("PE", "0"),
                                sr_support=raw_call.get("SR", "0"),
                            )
                        )

                # Add transcript information:
                gmaf = None
                if vep_string:
                    for transcript_info in vep_info:
                        transcript = self._get_vep_transcripts(transcript_info)
                        gmaf_raw = transcript_info.get("GMAF")
                        if gmaf_raw:
                            gmaf = float(gmaf_raw.split(":")[-1])
                        variant.add_transcript(transcript)

                if gmaf:
                    variant.add_frequency("GMAF", gmaf)
                    if not variant.thousand_g:
                        variant.thousand_g = gmaf

                elif snpeff_string:
                    for transcript_info in snpeff_info:
                        transcript = self._get_snpeff_transcripts(transcript_info)
                        variant.add_transcript(transcript)

                variant["most_severe_consequence"] = get_most_severe_consequence(variant["transcripts"])

                for gene in self._get_genes(variant):
                    variant.add_gene(gene)

                self._add_compounds(variant=variant, info_dict=info_dict)

                yield variant
Exemple #6
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def father(ctx):
    """Check number of variants in common"""
    logger.info("Running variant_integrity father version {0}".format(
        variant_integrity.__version__))
    
    print_columns = ['ind_id', 'fraction_of_common_variants', 'common_variants', 'number_calls']
    # Children is a dictionary of children that counts the number of errors
    duos = []
    children = {}
    analysis_individuals = set()
    
    for ind_id in ctx.parent.individuals:
        individual_object = ctx.parent.individuals[ind_id]
        if individual_object.father != '0':
            duo = {
                'child': ind_id,
                'father': individual_object.father
            } 
            
            analysis_individuals.add(ind_id)
            analysis_individuals.add(individual_object.father)
            
            duos.append(duo)
            logger.info("Duo found: {0}".format(
                ', '.join(list(duo.values()))
            ))
    
    logger.info("Individuals included in analysis: {0}".format(
                    ','.join(list(analysis_individuals))))
    
    for duo in duos:
        children[duo['child']] = dict(zip(
            print_columns, [duo['child'], 0, 0, 0]))
    
    
    for line in ctx.parent.variant_file:
        variant_dict = get_variant_dict(
            variant_line=line, 
            header_line=ctx.parent.header_line
        )
        
        logger.debug("Checking genotype calls for variant {0}".format(
            get_variant_id(variant_dict=variant_dict)
        ))
        
        genotypes = get_genotypes(variant_dict, analysis_individuals)
        
        for duo in duos:
            child_id = duo['child']
            child_genotype = genotypes[child_id]
            father_genotype = genotypes[duo['father']]
            duo_genotypes = [
                child_genotype,
                father_genotype
            ]
            #First check if the child has the variant:
            if child_genotype.has_variant:
                # If child have high quality we count the variant
                if check_high_quality([child_genotype], ctx.parent.gq_treshold):
                    children[child_id]['number_calls'] += 1
                    if check_common_variant(duo_genotypes):
                        children[child_id]['common_variants'] += 1
    
    results = []
    
    for child_id in children:
        child_info = children[child_id]
        common = child_info['common_variants']
        variants = child_info['number_calls']
        percentage = common/variants
        
        child_info['fraction_of_common_variants'] = round(percentage, 3)
        results.append(child_info)
    
    to_json = ctx.parent.to_json
    outfile = ctx.parent.outfile
    
    if to_json:
        if outfile:
            json.dump(results, outfile)
        else:
            print(json.dumps(results))
    else:
        if outfile:
            outfile.write("#{0}\n".format('\t'.join(print_columns)))
        else:
            print("#{0}".format('\t'.join(print_columns)))
        
        for result in results:
            print_line = "{0}\t{1}\t{2}\t{3}".format(
                    result['ind_id'], result['fraction_of_common_variants'],
                    result['common_variants'], result['number_calls']
                )
            if outfile:
                outfile.write("{0}\n".format(print_line))
            else:
                print(print_line)
Exemple #7
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def mendel(ctx):
    """Check mendelian errors in all trios"""
    logger.info("Running variant_integrity mendel {0}".format(
        variant_integrity.__version__))
    
    print_columns = ['ind_id', 'fraction_of_errors', 'mendelian_errors', 'number_calls']
    # Children is a dictionary of children that counts the number of errors
    trios = []
    children = {}
    analysis_individuals = set()
    
    for family in ctx.parent.families:
        family_object = ctx.parent.families[family]
        for trio in family_object.trios:
            trio_individuals = {
                'mother':None,
                'father':None,
                'child':None,
            }
            for ind_id in trio:
                analysis_individuals.add(ind_id)
                individual_object = ctx.parent.individuals[ind_id]
                if individual_object.mother in trio:
                    trio_individuals['child'] = ind_id
                elif individual_object.sex == 1:
                    trio_individuals['father'] = ind_id
                else:
                    trio_individuals['mother'] = ind_id
            trios.append(trio_individuals)
            logger.info("Trio found: {0}".format(
                ', '.join(list(trio_individuals.values()))
            ))
    
    logger.info("Individuals included in analysis: {0}".format(
                    ','.join(list(analysis_individuals))))
    
    for trio in trios:
        children[trio['child']] = dict(zip(
            print_columns, [trio['child'], 0, 0, 0]))
    
    
    for line in ctx.parent.variant_file:
        variant_dict = get_variant_dict(
            variant_line=line, 
            header_line=ctx.parent.header_line
        )
        
        logger.debug("Checking genotype calls for variant {0}".format(
            get_variant_id(variant_dict=variant_dict)
        ))
        
        genotypes = get_genotypes(variant_dict, analysis_individuals)
        
        for trio in trios:
            child_id = trio['child']
            child_genotype = genotypes[child_id]
            mother_genotype = genotypes[trio['mother']]
            father_genotype = genotypes[trio['father']]
            trio_genotypes = [
                child_genotype,
                mother_genotype,
                father_genotype
            ]
            #First check if the child has the variant:
            if child_genotype.has_variant:
                # If all individuals are high quality we count the variant
                if check_high_quality(trio_genotypes, ctx.parent.gq_treshold):
                    children[child_id]['number_calls'] += 1
                    if check_mendelian_error(child_genotype, mother_genotype, father_genotype):
                        children[child_id]['mendelian_errors'] += 1
    
    results = []
    
    for child_id in children:
        child_info = children[child_id]
        errors = child_info['mendelian_errors']
        variants = child_info['number_calls']
        percentage = errors/variants
        
        child_info['fraction_of_errors'] = round(percentage, 3)
        results.append(child_info)
    
    to_json = ctx.parent.to_json
    outfile = ctx.parent.outfile
    
    if to_json:
        if outfile:
            json.dump(results, outfile)
        else:
            print(json.dumps(results))
    else:
        if outfile:
            outfile.write("#{0}\n".format('\t'.join(print_columns)))
        else:
            print("#{0}".format('\t'.join(print_columns)))
        
        for result in results:
            print_line = "{0}\t{1}\t{2}\t{3}".format(
                    result['ind_id'], result['fraction_of_errors'],
                    result['mendelian_errors'], result['number_calls']
                )
            if outfile:
                outfile.write("{0}\n".format(print_line))
            else:
                print(print_line)
Exemple #8
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    def _formated_variants(self, raw_variants, case_obj):
        """Return variant objects

            Args:
                raw_variants (Iterable): An iterable with variant lines
                case_obj (puzzle.nodels.Case): A case object

        """
        vcf_file_path = case_obj.variant_source

        logger.info("Parsing file {0}".format(vcf_file_path))
        head = HeaderParser()
        handle = get_vcf_handle(infile=vcf_file_path)
        # Parse the header
        for line in handle:
            line = line.rstrip()
            if line.startswith('#'):
                if line.startswith('##'):
                    head.parse_meta_data(line)
                else:
                    head.parse_header_line(line)
            else:
                break

        handle.close()

        header_line = head.header

        # Get the individual ids for individuals in vcf file
        vcf_individuals = set([ind_id for ind_id in head.individuals])

        variant_columns = ['CHROM', 'POS', 'ID', 'REF', 'ALT', 'QUAL', 'FILTER']

        vep_header = head.vep_columns
        snpeff_header = head.snpeff_columns

        index = 0
        for variant_line in raw_variants:
            if not variant_line.startswith('#'):
                index += 1
                #Create a variant dict:
                variant_dict =  get_variant_dict(
                    variant_line = variant_line,
                    header_line = header_line
                )
                variant_dict['CHROM'] = variant_dict['CHROM'].lstrip('chrCHR')
                #Crreate a info dict:
                info_dict = get_info_dict(
                    info_line = variant_dict['INFO']
                )
                #Check if vep annotation:
                vep_string = info_dict.get('CSQ')

                #Check if snpeff annotation:
                snpeff_string = info_dict.get('ANN')

                if vep_string:
                    #Get the vep annotations
                    vep_info = get_vep_info(
                        vep_string = vep_string,
                        vep_header = vep_header
                    )

                elif snpeff_string:
                    #Get the vep annotations
                    snpeff_info = get_snpeff_info(
                        snpeff_string = snpeff_string,
                        snpeff_header = snpeff_header
                    )

                variant = Variant(
                    **{column: variant_dict.get(column, '.')
                        for column in variant_columns}
                    )

                logger.debug("Creating a variant object of variant {0}".format(
                    variant.get('variant_id')))

                variant['index'] = index
                logger.debug("Updating index to: {0}".format(
                    index))

                variant['start'] = int(variant_dict['POS'])


                if self.variant_type == 'sv':
                    other_chrom = variant['CHROM']
                    # If we have a translocation:
                    if ':' in variant_dict['ALT']:
                        other_coordinates = variant_dict['ALT'].strip('ACGTN[]').split(':')
                        other_chrom = other_coordinates[0].lstrip('chrCHR')
                        other_position = other_coordinates[1]
                        variant['stop'] = other_position

                        #Set 'infinity' to length if translocation
                        variant['sv_len'] = float('inf')
                    else:
                        variant['stop'] = int(info_dict.get('END', variant_dict['POS']))
                        variant['sv_len'] = variant['stop'] - variant['start']

                    variant['stop_chrom'] = other_chrom

                else:
                    variant['stop'] = int(variant_dict['POS']) + \
                        (len(variant_dict['REF']) - len(variant_dict['ALT']))

                variant['sv_type'] = info_dict.get('SVTYPE')
                variant['cytoband_start'] = get_cytoband_coord(
                                                chrom=variant['CHROM'],
                                                pos=variant['start'])
                if variant.get('stop_chrom'):
                    variant['cytoband_stop'] = get_cytoband_coord(
                                                chrom=variant['stop_chrom'],
                                                pos=variant['stop'])

                # It would be easy to update these keys...
                thousand_g = info_dict.get('1000GAF')
                if thousand_g:
                    logger.debug("Updating thousand_g to: {0}".format(
                        thousand_g))
                    variant['thousand_g'] = float(thousand_g)
                    variant.add_frequency('1000GAF', variant.get('thousand_g'))

                #SV specific tag for number of occurances
                occurances = info_dict.get('OCC')
                if occurances:
                    logger.debug("Updating occurances to: {0}".format(
                        occurances))
                    variant['occurances'] = float(occurances)
                    variant.add_frequency('OCC', occurances)

                cadd_score = info_dict.get('CADD')
                if cadd_score:
                    logger.debug("Updating cadd_score to: {0}".format(
                        cadd_score))
                    variant['cadd_score'] = float(cadd_score)

                rank_score_entry = info_dict.get('RankScore')
                if rank_score_entry:
                    for family_annotation in rank_score_entry.split(','):
                        rank_score = family_annotation.split(':')[-1]
                    logger.debug("Updating rank_score to: {0}".format(
                        rank_score))
                    variant['rank_score'] = float(rank_score)

                genetic_models_entry = info_dict.get('GeneticModels')
                if genetic_models_entry:
                    genetic_models = []
                    for family_annotation in genetic_models_entry.split(','):
                        for genetic_model in family_annotation.split(':')[-1].split('|'):
                            genetic_models.append(genetic_model)
                    logger.debug("Updating rank_score to: {0}".format(
                        rank_score))
                    variant['genetic_models'] = genetic_models

                #Add genotype calls:
                for individual in case_obj.individuals:
                    sample_id = individual.ind_id

                    if sample_id in vcf_individuals:

                        raw_call = dict(zip(
                            variant_dict['FORMAT'].split(':'),
                            variant_dict[sample_id].split(':'))
                        )
                        variant.add_individual(Genotype(
                            sample_id = sample_id,
                            genotype = raw_call.get('GT', './.'),
                            case_id = individual.case_name,
                            phenotype = individual.phenotype,
                            ref_depth = raw_call.get('AD', ',').split(',')[0],
                            alt_depth = raw_call.get('AD', ',').split(',')[1],
                            genotype_quality = raw_call.get('GQ', '.'),
                            depth = raw_call.get('DP', '.'),
                            supporting_evidence = raw_call.get('SU', '0'),
                            pe_support = raw_call.get('PE', '0'),
                            sr_support = raw_call.get('SR', '0'),
                        ))

                # Add transcript information:
                if vep_string:
                    for transcript in self._get_vep_transcripts(variant, vep_info):
                        variant.add_transcript(transcript)

                elif snpeff_string:
                    for transcript in self._get_snpeff_transcripts(variant, snpeff_info):
                        variant.add_transcript(transcript)

                variant['most_severe_consequence'] = get_most_severe_consequence(
                    variant['transcripts']
                )

                for gene in self._get_genes(variant):
                    variant.add_gene(gene)

                self._add_compounds(variant=variant, info_dict=info_dict)

                yield variant
Exemple #9
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    def _format_variant(self, variant_line, index, case_obj, head):
        """Return variant objects

            Args:
                raw_variants (Iterable): An iterable with variant lines
                case_obj (puzzle.nodels.Case): A case object

        """
        header_line = head.header

        # Get the individual ids for individuals in vcf file
        vcf_individuals = set([ind_id for ind_id in head.individuals])

        variant_columns = ['CHROM', 'POS', 'ID', 'REF', 'ALT', 'QUAL', 'FILTER']

        vep_header = head.vep_columns
        snpeff_header = head.snpeff_columns

        #Create a variant dict:
        variant_dict =  get_variant_dict(
            variant_line = variant_line,
            header_line = header_line
        )
        variant_dict['CHROM'] = variant_dict['CHROM'].lstrip('chrCHR')
        #Crreate a info dict:
        info_dict = get_info_dict(
            info_line = variant_dict['INFO']
        )
        #Check if vep annotation:
        vep_string = info_dict.get('CSQ')

        #Check if snpeff annotation:
        snpeff_string = info_dict.get('ANN')

        if vep_string:
            #Get the vep annotations
            vep_info = get_vep_info(
                vep_string = vep_string,
                vep_header = vep_header
            )

        elif snpeff_string:
            #Get the vep annotations
            snpeff_info = get_snpeff_info(
                snpeff_string = snpeff_string,
                snpeff_header = snpeff_header
            )

        variant = Variant(
            **{column: variant_dict.get(column, '.')
                for column in variant_columns}
            )

        logger.debug("Creating a variant object of variant {0}".format(
            variant.get('variant_id')))

        variant['index'] = index
        logger.debug("Updating index to: {0}".format(
            index))

        variant['start'] = int(variant_dict['POS'])


        if self.variant_type == 'sv':
            other_chrom = variant['CHROM']
            # If we have a translocation:
            if ':' in variant_dict['ALT'] and not '<' in variant_dict['ALT']:
                other_coordinates = variant_dict['ALT'].strip('ACGTN[]').split(':')
                other_chrom = other_coordinates[0].lstrip('chrCHR')
                other_position = other_coordinates[1]
                variant['stop'] = other_position

                #Set 'infinity' to length if translocation
                variant['sv_len'] = float('inf')
            else:
                variant['stop'] = int(info_dict.get('END', variant_dict['POS']))
                variant['sv_len'] = variant['stop'] - variant['start']

            variant['stop_chrom'] = other_chrom

        else:
            variant['stop'] = int(variant_dict['POS']) + \
                (len(variant_dict['REF']) - len(variant_dict['ALT']))

        variant['sv_type'] = info_dict.get('SVTYPE')
        variant['cytoband_start'] = get_cytoband_coord(
                                        chrom=variant['CHROM'],
                                        pos=variant['start'])
        if variant.get('stop_chrom'):
            variant['cytoband_stop'] = get_cytoband_coord(
                                        chrom=variant['stop_chrom'],
                                        pos=variant['stop'])

        # It would be easy to update these keys...
        thousand_g = info_dict.get('1000GAF')
        if thousand_g:
            logger.debug("Updating thousand_g to: {0}".format(
                thousand_g))
            variant['thousand_g'] = float(thousand_g)
            variant.add_frequency('1000GAF', variant.get('thousand_g'))

        #SV specific tag for number of occurances
        occurances = info_dict.get('OCC')
        if occurances:
            logger.debug("Updating occurances to: {0}".format(
                occurances))
            variant['occurances'] = float(occurances)
            variant.add_frequency('OCC', occurances)

        cadd_score = info_dict.get('CADD')
        if cadd_score:
            logger.debug("Updating cadd_score to: {0}".format(
                cadd_score))
            variant['cadd_score'] = float(cadd_score)

        rank_score_entry = info_dict.get('RankScore')
        if rank_score_entry:
            for family_annotation in rank_score_entry.split(','):
                rank_score = family_annotation.split(':')[-1]
            logger.debug("Updating rank_score to: {0}".format(
                rank_score))
            variant['rank_score'] = float(rank_score)

        genetic_models_entry = info_dict.get('GeneticModels')
        if genetic_models_entry:
            genetic_models = []
            for family_annotation in genetic_models_entry.split(','):
                for genetic_model in family_annotation.split(':')[-1].split('|'):
                    genetic_models.append(genetic_model)
            logger.debug("Updating rank_score to: {0}".format(
                rank_score))
            variant['genetic_models'] = genetic_models

        #Add genotype calls:
        for individual in case_obj.individuals:
            sample_id = individual.ind_id

            if sample_id in vcf_individuals:

                raw_call = dict(zip(
                    variant_dict['FORMAT'].split(':'),
                    variant_dict[sample_id].split(':'))
                )

                genotype = Genotype(**raw_call)

                variant.add_individual(puzzle_genotype(
                    sample_id = sample_id,
                    genotype = genotype.genotype,
                    case_id = individual.case_name,
                    phenotype = individual.phenotype,
                    ref_depth = genotype.ref_depth,
                    alt_depth = genotype.alt_depth,
                    genotype_quality = genotype.genotype_quality,
                    depth = genotype.depth_of_coverage,
                    supporting_evidence = genotype.supporting_evidence,
                    pe_support = genotype.pe_support,
                    sr_support = genotype.sr_support,
                ))

        # Add transcript information:
        gmaf = None
        if vep_string:
            for transcript_info in vep_info:
                transcript = self._get_vep_transcripts(transcript_info)
                gmaf_raw = transcript_info.get('GMAF')
                if gmaf_raw:
                    gmaf = float(gmaf_raw.split(':')[-1])
                variant.add_transcript(transcript)

        if gmaf:
            variant.add_frequency('GMAF', gmaf)
            if not variant.thousand_g:
                variant.thousand_g = gmaf

        elif snpeff_string:
            for transcript_info in snpeff_info:
                transcript = self._get_snpeff_transcripts(transcript_info)
                variant.add_transcript(transcript)

        most_severe_consequence = get_most_severe_consequence(
            variant['transcripts']
        )
        if most_severe_consequence:
            variant['most_severe_consequence'] = most_severe_consequence

            variant['impact_severity'] = IMPACT_SEVERITIES.get(most_severe_consequence)

        for gene in self._get_genes(variant):
            variant.add_gene(gene)

        self._add_compounds(variant=variant, info_dict=info_dict)

        return variant