We further investigated the potential functional effects of individual variation in the context of ENCODE annotations. We divided NA12878 variants into common and rare classes, and partitioned these into those overlapping ENCODE annotation (Figure 9A, Supplementary Tables K1 and K2). We also predicted potential functional effects: for protein-coding genes, these are either non-synonymous SNPs or variants likely to induce loss of function by frame-shift, premature stop, or splice-site disruption; for other regions, these are variants that overlap a TF-binding site. We found similar numbers of potentially functional variants affecting protein-coding genes or affecting other ENCODE annotations, suggesting that many functional variants within individual genomes lie outside exons of protein-coding genes. A more detailed analysis of regulatory variant annotation is described in ref 74.
