Table 3 Classification criteria for variants by impact and minor allele frequency

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