Fig. 4: Transcript-expression based annotation aids Mendelian variant interpretation.

a, Comparison of the proportion of high-quality pLoF variants filtered in a curated list of 61 haploinsufficient developmental delay genes in gnomAD versus ClinVar with a cut-off value of average pext across GTEx ≤ 0.1 (low expression). Expression-based filtering results in removal of 22.8% of gnomAD pLoFs and 3.8% of confidently curated set of pLoFs in ClinVar. b, Expression-based annotation filters 30% of pLoF variants found in gnomAD in a homozygous state in at least one individual, and 3.2% of any pLoF variants found in the same genes in ClinVar. c, We extended this filtering approach to pLoF and synonymous variants in gnomAD pLoF-intolerant genes (defined by LOEUF < 0.35). This filters 16.8% of LoF and 5.2% of synonymous variants. The total number of high-quality variants considered in each group is shown. For all pLoFs only high-confidence LOFTEE variants were considered. P values were determined by two-sided Fisher’s exact test for counts.