Table 3.

Classification criteria for variants by impact and minor allele frequency

	Consequence	Pathogenicity	Minor allele frequency	Number of variants
Meaning	The effect of the mutation on the protein	How likely the mutation is to impair protein function	How rare the alternative allele is in the population
Source	Ensembl, ReMM	CADD, Sutr, SpliceAI	gnomAD, 1000G, TOPMed, ESP6500
High impact	5′ UTR variants, splice site mutation, stop gain or loss, start loss, insertion, deletion, duplication, missense variants and variants in mature miRNAs	CADD > 25 or Sutr > 1 (for 5′ UTR variants only) or SpliceAI score > 0.5 (for splice site variants only)	<0.005	1,141,302
			<0.01	1,151,111
			<0.05	1,160,767
			<0.1	1,162,399
			<0.2	1,163,464
			<1	1,165,167
Low impact	All consequences except for intergenic and intronic variants, variants in transcripts subject to nonsense-mediated decay, and variants up- or downstream of a gene; all variants with a ReMM score > 0.95	Not assessed	<0.1	6,398,787