The impact scores for ncSNPs consist of two parts: a functional element score and a mutation effect score. The functional element score reflects how likely it is that the SNP is located in a functional region of the genome, and the mutation effect score estimates how likely a mutation at this position is to affect the function of an overlapping region. Any ncSNP that overlaps a known functional element in the UCSC Mouse Genome Browser (mm10, GRCm38 assembly38) receives a functional element score of 1. Functional elements are defined using the following gene regulation tracks: open regulatory annotation (ORegAnno) elements, the NHGRI's bi-directional promoters, and Repressor Element 1-Silencing Transcription Factor (REST) binding sites, as well as conserved elements as predicted by the phastCons program (conservation track) (ref. 47). Furthermore, ncSNPs overlapping a predicted conserved element were assigned the element's phastCons score. The mutation score is based on the evolutionary conservation of the position in alignments with other placental mammals. The phyloP package (ref. 48) was used to estimate conservation. The ncSNP impact score is the product of the functional element
