GnomAD SVs v4 - discrepancy between hemizygote & male (XY) counts

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.
gnomAD0

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 :slight_smile:

Yeah, that could be an issue, but DMD is not located to a PAR.

1 Like

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.

1 Like

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