. 2017 Nov 15;1(12):1507–1526. doi: 10.1210/js.2017-00330

Table 2.

Gene-Level Estimates of Cumulative Rare Nonsynonymous SNV Carrier Frequencies in the Control Cohort

Gene	Protein Size (AAs)	SNV Group:  AF <0.5%		SNV Group:  AF <0.05%		SNV Group: Singleton
Gene	Protein Size (AAs)	Population Frequency (%)	Number Needed to Sequence (n)	Population Frequency (%)	Number Needed to Sequence (n)	Population Frequency (%)	Number Needed to Sequence (n)
CHD7	2997	5.2	19	3.0	34	0.9	115
NF1	2839	2.1	47	1.5	67	0.5	187
GNAS	1037	2.6	38	1.4	71	0.5	208
KIF1B	1770	2.0	51	1.2	81	0.4	226
RET	1114	3.0	34	1.4	71	0.4	231
ARMC5	935	2.8	35	1.2	82	0.3	289
EPAS1	870	2.1	47	1.1	87	0.3	310
CASR	1078	1.5	67	0.7	149	0.3	354
FH	510	0.9	117	0.5	191	0.3	392
VHL^a	213	0.7	138	0.5	206	0.2	429
GHR	638	1.7	58	0.7	141	0.2	474
PRLR	622	1.6	61	0.5	190	0.2	504
PHEX^b	749	0.8	132	0.5	199	0.2	514
SDHA	664	1.3	78	0.9	110	0.2	516
KAL1^b	680	2.4	42	0.8	131	0.2	536
EGLN1^a	426	0.6	180	0.3	294	0.2	545
GATA3	444	0.5	181	0.3	286	0.2	644
MEN1	615	0.4	254	0.4	270	0.1	658
KCNJ5	419	0.5	195	0.4	228	0.1	734
GPR101^b	508	2.0	50	0.7	138	0.1	809
FGF23	251	0.5	213	0.3	288	0.1	891
AIP	330	1.4	70	0.4	272	0.1	923
THRB	461	0.6	156	0.3	379	0.1	963
THRA_2^c	490	0.3	283	0.3	367	0.1	1034
SDHB	280	0.6	168	0.4	319	0.1	1048
CDKN1B	198	0.9	109	0.4	264	0.1	1124
CDC73	531	0.2	468	0.2	468	0.1	1208
TMEM127^a	238	0.4	258	0.2	544	0.1	1217
CDKN2B	138	0.6	161	0.2	439	0.1	1336
THRA_1^c	410	0.2	517	0.1	679	0.1	1509
PRKAR1A	381	0.2	432	0.1	828	0.1	1514
GNA11	359	0.1	691	0.1	802	0.1	1594
CDKN1A	164	1.4	69	0.3	358	0.1	1598
SDHAF2	166	0.4	227	0.2	502	0.05	1890
SDHD	159	0.2	433	0.1	659	0.04	2245
CDKN2C	168	0.2	593	0.1	728	0.04	2302
SDHC	169	0.2	625	0.2	625	0.04	2757
MAX	160	0.1	837	0.1	1380	0.03	3318
AP2S1	142	0.01	12,066	0.01	12,066	0.01	12,066

The number needed to sequence (NNS) equates to the mean number of individuals (reported to the nearest whole number) requiring sequencing to identify a rare variant of each type (i.e., AF <0.5%, AF <0.05%, or singleton). This was determined by taking the reciprocal of the estimated cumulative variant frequency for each category of rare variant per individual (i.e., taking into account the presence of two alleles per gene). Genes are arranged in decreasing frequency of singleton variants.

Abbreviation: AA, amino acid.

^{^a}

Missing data for part of gene and/or reduced reliability of estimates due to reduced exon coverage.

^{^b}

For X-linked disorders, the NNS is stated for females (i.e., accounting for each allele).

^{^c}

Two transcripts are reported for THRA as described in the footnote in Table 1.