Greetings gnomAD CNV team,
First, thank you for all your hard work, and for the roll out of gnomAD SVs v4.
Recently we have noticed a discrepancy in the numbers between hemizygote counts and male (XY) counts on the X-chromosome.
For example in the DMD gene:
E.g. the number of males (XY) with the variant e.g. in the African subpopulation is ‘81’ (indicated as homozygotes), while the number of hemizygotes is ‘0’.
Is it intended to be this way, or is this a bug (which can be perhaps easily fixed)?
Thank you for looking into it,
Gyorgy
Had the same observation recently for some SNVs:
tabix https://storage.googleapis.com/gcp-public-data--gnomad/release/4.1/vcf/exomes/gnomad.exomes.v4.1.sites.chrX.vcf.bgz chrX:284193-284193 | grep "\sT\sC\s" | tr ';' '\n' | grep '^AC_XY' AC_XY=531069
vs.
gnomAD → 0
for me it turned out that the mismatch between hemizygous count on gnomad website and AC_XY field is coming from PAR regions… checking for the INFO flag non_par helps 
Yeah, that could be an issue, but DMD is not located to a PAR.
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Hello all,
We’ve just pushed a fix for the discrepancy for structural variants, those should now show the correct data. We’re continuing to look into the short-variant case.
Best, Phil
I’ve checked a number of short variants outside of the PARs and it looks like the hemizygote count matches the XY count in each case. Thanks for bringing these to our attention.
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Hi Phil,
Thank you for looking into this.
Yes, it looks like the hemizygote number matches the XY number now in every cell (green highlights).
However, there seems to be one more discrepancy. There are some homozygotes displayed for males (which doesn’t make sense), and it also gets counted into the overall number of homozygotes (see yellow highlights). This only seems to be a problem for CNVs (and not for SNVs) on the X chromosome.
Could you please check on this?
Thanks,
Gyorgy
The issue was partially fixed (on Jun 27-28), but it remained partly erroneous. I asked again here to fix it, but nothing happened, so I’ve posted the remaining part of the error (i.e. on Sep. 3: GnomAD SVs v4, X-chromosome: homozygous males) as a new topic, to make sure it’s not getting considered to be already fixed. Can someone pls look into it?
Hi Phil,
Can you pls check out this CNV on the X-chromosome:
The number of homozygotes still seems to be erroneous, i.e. statistically highly unlikely (i.e. practically impossible) to expect this high number of homozygotes based on the reported allele counts (i.e. 158 total alleles, consisting of 63 homozygotes, 25 hemizygotes and 7 calculated heterozygotes). Therefore, based on the number of hemizygotes it is plausible that the reported number of ‘homozygotes’ in reality represents almost exclusively ‘heterozygous’ occurrences.
Thank you,
Gyorgy
@browser_team @browser_team
Any chance to take a look at this?
