A coding SNP, be it synonymous or non-synonymous, may disturb the binding sites of an exonic splicing enhancer or silencer. In this case, the SNP may regulate alternative splicing and will be classified as ‘splicing regulation.’ If the alternative splicing further abolishes a domain of the translated protein due to exon skipping, then we classify such a SNP as ‘splicing regulation, abolishing protein domain’ and assign it a high-risk ranking. A ‘sense/synonymous’ SNP that does not affect any motif or protein structure will be assigned a low-risk ranking.
