Fig. 1

Number of 1KGP individuals indicated affected for screened IEMs by ClinVar or HGMD over time. A Number of screened IEM variants present in ClinVar or HGMD in 2014 and 2020. B Ancestry composition of individuals in 1KGP. C–F Bars are colored by ancestry as shown in B. Tick marks on bars cluster individuals by the variant classified as pathogenic that they harbor. Dashed black lines indicate the aggregate population incidence of screened IEMs. C The number of 1KGP individuals with an implied pathogenic genotype for a variant in Select ClinVar, defined as variants with a P classification with at least 1 review star. Variants that also have conflicting classifications (with VUS or B/LB) with 1 or more review stars are removed. D The number of 1KGP individuals with an implied pathogenic genotype for a variant in Full ClinVar, defined as variants with a P or LP classification. Variants that also have conflicting classifications (with VUS or B/LB) are removed. E The number of 1KGP individuals with an implied pathogenic genotype for a variant in Select HGMD variants, defined as variants classified as DM. 2014, 2016, and 2020 are shown because they are the years for which we have archived HGMD data. F The number of 1KGP individuals with an implied pathogenic genotype for a variant in Full HGMD variants, defined as variants classified as DM or DM?. G The number of affected individuals relative to the number of variants classified in each variant set. This approximates a false-positive rate, which has fallen over time for each database. *Data not available because the existing review star framework was not in place until 2015