degenerate type (0, 2, or 3), AA position as to the protein, coding sequence (CDS) strand (1 or ), estimated nonsynonymous-to- synonymous-rate ratio (o, reported by LRT), PhyloP score, PhyloP prediction, SIFT score, SIFT prediction, Polyphen2 score, Polyphen2 prediction, LRT score, LRT prediction, MutationTaster score, MutationTaster prediction. If any of the PhyloP, SIFT, Polyphen2, LRT, and MutationTaster scores were missing, their imputed scores (see Missing Data and Imputation) were reported (but their corresponding predictions will be ‘‘NA’’). There are a total of 75,931,005 entries for 64,646,969 unique NSs, each of which is defined as a unique combination of physical position and alternative allele. This is due to the fact that the same NS may be annotated by CCDS multiple times for different forms of the same gene. The numbers of nonmissing entries of NS, hg19 position, PhyloP score, SIFT score, Polyphen2 score, LRT score, and MutationTaster score per chromosome are summarized in Table 1. Because all scores (PhyloP, SIFT, Polyphen2, LRT, and MutationTaster) were scaled to [0, 1] with a larger score corresponding to higher conservation (PhyloP and LRT) or more likely to be deleterious (SIFT, Polyphen2, and MutationTaster), we can easily compare their distributions. Figure 1 shows the histograms of their total scores in different score ranges. An interesting observation is that all five methods show some form of bimodal distribution, with the majority of the scores clustered around 1 and a small proportion of the scores clustered around 0. The predictions from Polyphen2 and MutationTaster are more balanced, which have about 30% of the scores in range [0, 0.1), whereas the remaining three only have less than 7% scores in that range. Correspondingly, SIFT, LRT, and MutationTaster all predict more than half of the total NSs being deleterious, whereas Polyphen2 predicts that slightly less than half of the NSs are deleterious (Table 2). The proportion of pairwise agreement between methods on whether aN NS is deleterious is around 60–70%, with the highest agreement between the LRT and MutationTaster (77.19%) (Table 3). The Spearman’s rank correlation coefficients (RCCs) between scores of different Number of Entries in dbNSFP NS 8329939 5115071 4280786 2868872 3484907 4075171 3268295 2597009 3164462 3273027 4253046 3852960 1420096 2494133 2470042 2970643 4372234 1178377 4415600 2103098 989231 1553703 3176068 224235 75931005 64646969 hg19 8329939 5115063 4280782 2868872 3484907 4075036 3268295 2597009 3164462 3273027 4253046 3852960 1420096 2494133 2469767 2970643 4372095 1178377 4415600 2103098 989231 1553703 3176068 224235 75930444 64646408 PhyloP 8329796 5114264 4280786 2868872 3484907 4075171 3267997 2597009 3164462 3273027 4253046 3852960 1420096 2494133 2470042 2970623 4371639 1178377 4415600 2103098 989231 1553703 3175174 223727 75927740 64643749 SIFT 7611044 4376414 3804983 2532905 3134219 3710396 2819288 2278629 2893822 2924577 3793927 3412527 1278533 2262099 2206987 2589515 3943103 1031129 3916565 1935033 843131 1388173 2941495 205265 67833759 57471955 Polyphen2 7279405 4428042 3756644 2554593 3043592 3586226 2856409 2207857 2842191 2922389 3795848 3332085 1235036 2236525 2219513 2545952 3822645 1039874 3779650 1881731 842902 1338949 2719583 195144 66462785 56620320 LRT 7644552 4765076 4063236 2752943 3207583 3824055 2989039 2456441 2902636 3093339 4004874 3698888 1378650 2383704 2317477 2794456 4019068 1090517 3360865 1998568 890113 1444075 2834074 138312 70052541 59419546 Figure 1. Distributions of PhyloP, SIFT, Polyphen2, LRT, and MutationTaster scores. Table 2. Method Unknown/missing Nondeleterious Deleterious Summary of Predictions SIFT 8097246 31166227 36667532 Polyphen2 9468220 35477555 30985230 LRT 10556339 25950325 39424341 MutationTaster 3961293 29158468 42811244 Table 3. Pairwise Prediction Agreement Percentages (Upper Right Triangle) and Spearman’s Rank Correlation Coefficients (Lower Left Triangle) Method PhyloP SIFT Polyphen2 LRT MutationTaster PhyloP – 0.189 0.306 0.475 0.389 SIFT – – 0.517 0.267 0.313 Polyphen2 – 68.82 – 0.457 0.444 LRT – 62.14 66.82 – 0.618 MutationTaster – 61.69 64.91 77.19 – MutationTaster 7959066 4858487 4098445 2766053 3347045 3803359 3132425 2539459 2860881 2956250 4098876 3723502 1374240 2432185 2351630 2864645 4228681 1131942 3983007 1927606 925335 1461233 2998558 146802 71969712 61277012 Table 1. Chromosome 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X Y Total Total (unique)a 896 aNSs with the same position and alternative allele were counted only once. HUMAN MUTATION, Vol. 32, No. 8, 894–899, 2011