sites predicted by at least two of the three applicable methods (fig. S13) to be putatively functional. In total, 16.9% of SNVs (85,224) meet this criteria, of which 81,170 were nonsynonymous SNVs. About 95.7% (81,555) of all SNVs conservatively predicted to be functional were rare, and the odds ratio (OR) that rare variants are functional compared with variants with a MAF > 0.5% is 4.2 [95% confidence interval (CI) from 4.0 to 4.3; Fisher's exact test; P < 10−15), underscoring the potential impact of rare variants on health-related traits.
