Not exactly an MNV question, but I was wondering why for the same chromosome and start and end positions, gnomAD v4.1.0 sometimes lists multiple ref alleles. For example, when I use pytabix to query the chr 22 joint exomes and genomes vcf file for variants at position 10522592, I see that both A and G are possible ref alleles. I understand that a given locus can have multiple ALT alleles, but is the listing of multiple ref alleles due to the representation of alternate haplotype loci in GRCh38? Thank you so much!
Thanks for reaching out. I checked the chr22 joint VCF and did not see multiple reference alleles; the only reference allele listed in that file is G. For example, here is one of the records in that file:
#CHROM POS ID REF ALT QUAL FILTER INFO
chr22 10522592 . G T . GENOMES_FILTERED AC_joint=0;AN_joint=100756;AF_joint=0.00000;AC_genomes=0;AN_genomes=100756;AF_genomes=0.00000;genomes_filters=AC0,AS_VQSR;AC_joint_XX=0;AF_joint_XX=0.00000;AN_joint_XX=52314;nhomalt_joint_XX=0;AC_joint_XY=0;AF_joint_XY=0.00000;AN_joint_XY=48442;nhomalt_joint_XY=0;nhomalt_joint=0;AC_joint_afr_XX=0;AF_joint_afr_XX=0.00000;AN_joint_afr_XX=16804;nhomalt_joint_afr_XX=0;AC_joint_afr_XY=0;AF_joint_afr_XY=0.00000;AN_joint_afr_XY=14556;nhomalt_joint_afr_XY=0;AC_joint_afr=0;AF_joint_afr=0.00000;AN_joint_afr=31360;nhomalt_joint_afr=0;AC_joint_ami_XX=0;AF_joint_ami_XX=0.00000;AN_joint_ami_XX=274;nhomalt_joint_ami_XX=0;AC_joint_ami_XY=0;AF_joint_ami_XY=0.00000;AN_joint_ami_XY=294;nhomalt_joint_ami_XY=0;AC_joint_ami=0;AF_joint_ami=0.00000;AN_joint_ami=568;nhomalt_joint_ami=0;AC_joint_amr_XX=0;AF_joint_amr_XX=0.00000;AN_joint_amr_XX=4074;nhomalt_joint_amr_XX=0;AC_joint_amr_XY=0;AF_joint_amr_XY=0.00000;AN_joint_amr_XY=4908;nhomalt_joint_amr_XY=0;AC_joint_amr=0;AF_joint_amr=0.00000;AN_joint_amr=8982;nhomalt_joint_amr=0;AC_joint_asj_XX=0;AF_joint_asj_XX=0.00000;AN_joint_asj_XX=1228;nhomalt_joint_asj_XX=0;AC_joint_asj_XY=0;AF_joint_asj_XY=0.00000;AN_joint_asj_XY=1078;nhomalt_joint_asj_XY=0;AC_joint_asj=0;AF_joint_asj=0.00000;AN_joint_asj=2306;nhomalt_joint_asj=0;AC_joint_eas_XX=0;AF_joint_eas_XX=0.00000;AN_joint_eas_XX=1850;nhomalt_joint_eas_XX=0;AC_joint_eas_XY=0;AF_joint_eas_XY=0.00000;AN_joint_eas_XY=2256;nhomalt_joint_eas_XY=0;AC_joint_eas=0;AF_joint_eas=0.00000;AN_joint_eas=4106;nhomalt_joint_eas=0;AC_joint_fin_XX=0;AF_joint_fin_XX=0.00000;AN_joint_fin_XX=1292;nhomalt_joint_fin_XX=0;AC_joint_fin_XY=0;AF_joint_fin_XY=0.00000;AN_joint_fin_XY=4124;nhomalt_joint_fin_XY=0;AC_joint_fin=0;AF_joint_fin=0.00000;AN_joint_fin=5416;nhomalt_joint_fin=0;AC_joint_mid_XX=0;AF_joint_mid_XX=0.00000;AN_joint_mid_XX=96;nhomalt_joint_mid_XX=0;AC_joint_mid_XY=0;AF_joint_mid_XY=0.00000;AN_joint_mid_XY=98;nhomalt_joint_mid_XY=0;AC_joint_mid=0;AF_joint_mid=0.00000;AN_joint_mid=194;nhomalt_joint_mid=0;AC_joint_nfe_XX=0;AF_joint_nfe_XX=0.00000;AN_joint_nfe_XX=25264;nhomalt_joint_nfe_XX=0;AC_joint_nfe_XY=0;AF_joint_nfe_XY=0.00000;AN_joint_nfe_XY=18184;nhomalt_joint_nfe_XY=0;AC_joint_nfe=0;AF_joint_nfe=0.00000;AN_joint_nfe=43448;nhomalt_joint_nfe=0;AC_joint_raw=1;AF_joint_raw=7.39601e-06;AN_joint_raw=135208;nhomalt_joint_raw=0;AC_joint_remaining_XX=0;AF_joint_remaining_XX=0.00000;AN_joint_remaining_XX=656;nhomalt_joint_remaining_XX=0;AC_joint_remaining_XY=0;AF_joint_remaining_XY=0.00000;AN_joint_remaining_XY=624;nhomalt_joint_remaining_XY=0;AC_joint_remaining=0;AF_joint_remaining=0.00000;AN_joint_remaining=1280;nhomalt_joint_remaining=0;AC_joint_sas_XX=0;AF_joint_sas_XX=0.00000;AN_joint_sas_XX=776;nhomalt_joint_sas_XX=0;AC_joint_sas_XY=0;AF_joint_sas_XY=0.00000;AN_joint_sas_XY=2320;nhomalt_joint_sas_XY=0;AC_joint_sas=0;AF_joint_sas=0.00000;AN_joint_sas=3096;nhomalt_joint_sas=0;faf95_joint=0.00000;faf99_joint=0.00000;faf95_joint_afr=0.00000;faf99_joint_afr=0.00000;faf95_joint_amr=0.00000;faf99_joint_amr=0.00000;faf95_joint_eas=0.00000;faf99_joint_eas=0.00000;faf95_joint_mid=0.00000;faf99_joint_mid=0.00000;faf95_joint_nfe=0.00000;faf99_joint_nfe=0.00000;faf95_joint_sas=0.00000;faf99_joint_sas=0.00000;age_hist_het_bin_freq_joint=0|0|0|0|0|0|0|0|0|0;age_hist_het_n_smaller_joint=0;age_hist_het_n_larger_joint=0;age_hist_hom_bin_freq_joint=0|0|0|0|0|0|0|0|0|0;age_hist_hom_n_smaller_joint=0;age_hist_hom_n_larger_joint=0;gq_hist_alt_bin_freq_joint=0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0;gq_hist_all_bin_freq_joint=0|0|0|0|29875|7371|5291|2687|1255|1172|799|403|450|325|152|182|138|50|77|151;dp_hist_alt_bin_freq_joint=0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0;dp_hist_alt_n_larger_joint=0;dp_hist_all_bin_freq_joint=0|0|11627|15622|9366|6140|4410|1795|665|307|189|96|70|37|20|14|8|4|2|3;dp_hist_all_n_larger_joint=3;ab_hist_alt_bin_freq_joint=0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0;outside_broad_capture_region;outside_ukb_capture_region;outside_broad_calling_region;outside_ukb_calling_region;not_called_in_exomes;AC_genomes_XX=0;AF_genomes_XX=0.00000;AN_genomes_XX=52314;nhomalt_genomes_XX=0;AC_genomes_XY=0;AF_genomes_XY=0.00000;AN_genomes_XY=48442;nhomalt_genomes_XY=0;nhomalt_genomes=0;AC_genomes_afr_XX=0;AF_genomes_afr_XX=0.00000;AN_genomes_afr_XX=16804;nhomalt_genomes_afr_XX=0;AC_genomes_afr_XY=0;AF_genomes_afr_XY=0.00000;AN_genomes_afr_XY=14556;nhomalt_genomes_afr_XY=0;AC_genomes_afr=0;AF_genomes_afr=0.00000;AN_genomes_afr=31360;nhomalt_genomes_afr=0;AC_genomes_ami_XX=0;AF_genomes_ami_XX=0.00000;AN_genomes_ami_XX=274;nhomalt_genomes_ami_XX=0;AC_genomes_ami_XY=0;AF_genomes_ami_XY=0.00000;AN_genomes_ami_XY=294;nhomalt_genomes_ami_XY=0;AC_genomes_ami=0;AF_genomes_ami=0.00000;AN_genomes_ami=568;nhomalt_genomes_ami=0;AC_genomes_amr_XX=0;AF_genomes_amr_XX=0.00000;AN_genomes_amr_XX=4074;nhomalt_genomes_amr_XX=0;AC_genomes_amr_XY=0;AF_genomes_amr_XY=0.00000;AN_genomes_amr_XY=4908;nhomalt_genomes_amr_XY=0;AC_genomes_amr=0;AF_genomes_amr=0.00000;AN_genomes_amr=8982;nhomalt_genomes_amr=0;AC_genomes_asj_XX=0;AF_genomes_asj_XX=0.00000;AN_genomes_asj_XX=1228;nhomalt_genomes_asj_XX=0;AC_genomes_asj_XY=0;AF_genomes_asj_XY=0.00000;AN_genomes_asj_XY=1078;nhomalt_genomes_asj_XY=0;AC_genomes_asj=0;AF_genomes_asj=0.00000;AN_genomes_asj=2306;nhomalt_genomes_asj=0;AC_genomes_eas_XX=0;AF_genomes_eas_XX=0.00000;AN_genomes_eas_XX=1850;nhomalt_genomes_eas_XX=0;AC_genomes_eas_XY=0;AF_genomes_eas_XY=0.00000;AN_genomes_eas_XY=2256;nhomalt_genomes_eas_XY=0;AC_genomes_eas=0;AF_genomes_eas=0.00000;AN_genomes_eas=4106;nhomalt_genomes_eas=0;AC_genomes_fin_XX=0;AF_genomes_fin_XX=0.00000;AN_genomes_fin_XX=1292;nhomalt_genomes_fin_XX=0;AC_genomes_fin_XY=0;AF_genomes_fin_XY=0.00000;AN_genomes_fin_XY=4124;nhomalt_genomes_fin_XY=0;AC_genomes_fin=0;AF_genomes_fin=0.00000;AN_genomes_fin=5416;nhomalt_genomes_fin=0;AC_genomes_mid_XX=0;AF_genomes_mid_XX=0.00000;AN_genomes_mid_XX=96;nhomalt_genomes_mid_XX=0;AC_genomes_mid_XY=0;AF_genomes_mid_XY=0.00000;AN_genomes_mid_XY=98;nhomalt_genomes_mid_XY=0;AC_genomes_mid=0;AF_genomes_mid=0.00000;AN_genomes_mid=194;nhomalt_genomes_mid=0;AC_genomes_nfe_XX=0;AF_genomes_nfe_XX=0.00000;AN_genomes_nfe_XX=25264;nhomalt_genomes_nfe_XX=0;AC_genomes_nfe_XY=0;AF_genomes_nfe_XY=0.00000;AN_genomes_nfe_XY=18184;nhomalt_genomes_nfe_XY=0;AC_genomes_nfe=0;AF_genomes_nfe=0.00000;AN_genomes_nfe=43448;nhomalt_genomes_nfe=0;AC_genomes_raw=1;AF_genomes_raw=7.39601e-06;AN_genomes_raw=135208;nhomalt_genomes_raw=0;AC_genomes_remaining_XX=0;AF_genomes_remaining_XX=0.00000;AN_genomes_remaining_XX=656;nhomalt_genomes_remaining_XX=0;AC_genomes_remaining_XY=0;AF_genomes_remaining_XY=0.00000;AN_genomes_remaining_XY=624;nhomalt_genomes_remaining_XY=0;AC_genomes_remaining=0;AF_genomes_remaining=0.00000;AN_genomes_remaining=1280;nhomalt_genomes_remaining=0;AC_genomes_sas_XX=0;AF_genomes_sas_XX=0.00000;AN_genomes_sas_XX=776;nhomalt_genomes_sas_XX=0;AC_genomes_sas_XY=0;AF_genomes_sas_XY=0.00000;AN_genomes_sas_XY=2320;nhomalt_genomes_sas_XY=0;AC_genomes_sas=0;AF_genomes_sas=0.00000;AN_genomes_sas=3096;nhomalt_genomes_sas=0;faf95_genomes=0.00000;faf99_genomes=0.00000;faf95_genomes_afr=0.00000;faf99_genomes_afr=0.00000;faf95_genomes_amr=0.00000;faf99_genomes_amr=0.00000;faf95_genomes_eas=0.00000;faf99_genomes_eas=0.00000;faf95_genomes_nfe=0.00000;faf99_genomes_nfe=0.00000;faf95_genomes_sas=0.00000;faf99_genomes_sas=0.00000;age_hist_het_bin_freq_genomes=0|0|0|0|0|0|0|0|0|0;age_hist_het_n_smaller_genomes=0;age_hist_het_n_larger_genomes=0;age_hist_hom_bin_freq_genomes=0|0|0|0|0|0|0|0|0|0;age_hist_hom_n_smaller_genomes=0;age_hist_hom_n_larger_genomes=0;gq_hist_alt_bin_freq_genomes=0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0;gq_hist_all_bin_freq_genomes=0|0|0|0|29875|7371|5291|2687|1255|1172|799|403|450|325|152|182|138|50|77|151;dp_hist_alt_bin_freq_genomes=0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0;dp_hist_alt_n_larger_genomes=0;dp_hist_all_bin_freq_genomes=0|0|11627|15622|9366|6140|4410|1795|665|307|189|96|70|37|20|14|8|4|2|3;dp_hist_all_n_larger_genomes=3;ab_hist_alt_bin_freq_genomes=0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0
I can’t comment on how pytabix or external tools are parsing gnomAD data; our team recommends using Hail and our Hail utilities for gnomAD to parse gnomAD data.