Identify allele balance issues in bulk

General
1

For variants that exhibit less than ideal allele balance and/or depth of coverage, is there a way to identify these in bulk? These metrics may suggest dubious data quality but are not easily identifiable by way of a flag. For example, the allele balance for 2-47482876-T-G(GRCh38) looks to follow a normal distribution (data quality would be considered sufficient); 17-46171276-G-A(GRCh38) looks right-skewed (may require a closer look); 17-17796084-CG-C might be questionable. The AS_pab_max metric appears to be a proxy, but it may not be the most appropriate value.

Also, is the gnomAD team area of any gene regions, genes and/or exons that may have a preponderance of allele balance issues and/or questionable depth of coverage?

2

We recommend using our allele balance histogram. This annotation is present on our Hail Tables (documented in this help page) and VCFs (ab_hist_alt_bin_freq).

Regarding your second question: we flag variants that fall within low complexity regions or in regions with overlapping segmental duplications (described on this help page). Other genes that may not be sequenced well, including a subset of medically relevant genes, are described in this publication.