previously reported to be medically relevant32,33. We annotated variants that were identified in the GAsP dataset against the Human Gene Mutation Database (HGMD) disease-causing pathological and ClinVar pathogenic variants. This analysis identified 732 variants (686 SNPs and 46 insertions or deletions (indels)) in 514 genes (Fig. 3b, Supplementary Table 4b, c and Supplementary Information 11). We compared the 732 pathogenic variants against the gnomAD, ExAC29, 1000Genomes4, ESP30, dbSNP34, ALSPAC, TwinsUK35 and 1000Japanese6 databases to remove variants that occurred at >1%, focused on those with allele frequencies >0.15% in GAsP (38 variants), and reviewed them against the criteria defined by the American College of Medical Genetics (ACMG). This resulted in reclassification of 11 of the 38 variants (Supplementary Table 4d). We examined the geographical distribution of the remaining, revalidated but high-frequency, pathogenic disease-associated variants. As expected, most of these variants were highly enriched in Asia. For example, an HBB variant (chromosome 11: 5248155 c.92+5G>C) associated with β-thalassaemia is found almost exclusively in south Asians and at a lower frequency in southeast Asians (Fig. 3c).
