score of binding affinity change by calculating the log-odds (LOD) of probabilities of paired binding sites for each motif (m): To estimate the statistical significance of binding affinity change, we performed permutations of on 52 054 804 SNPs in dbSNP137 and computed respective LOD of all ENCODE motifs to form the null distribution of binding affinity difference. We then used FastPval (36) to compute the P-value of each LOD from aformentioned empirical distribution.