Table 2.

Frequency of MBD4 germline deleterious variants in the UM series compared with various populations of the GnomAD database^a

Study population		No. of LoF variants	Allele countc	Frequency	RRd(95% CIe)	Fisher test (P value)
UM consecutive series		7f	2186	0.00320	—	—
GnomAD v2.1.1	NFEb	47	113 736	0.00041	7.75 (3.51 to 17.12)	6.86 × 10−5
	Populationb	88	251 450	0.00035	9.15 (4.24 to 19.73)	2.00 × 10−5
GnomAD v2.1.1 (controls only)	NFE	13	42 768	0.00030	10.53 (4.20 to 26.38)	2.82 × 10−5
	General population	33	109 404	0.00030	10.62 (4.70 to 23.97)	1.16 × 10−5
GnomAD v2.1.1 (noncancer only)	NFE	41	102 730	0.00040	8.02 (3.60 to 17.86)	5.89 × 10−5
	General population	82	236 912	0.00035	9.25 (4.28 to 19.99)	1.90 × 10−5
GnomAD v3	NFE	20	64 571	0.00031	10.34 (4.38 to 24.42)	2.00 × 10−5
	General population	39	143 286	0.00027	11.76 (5.27 to 26.27)	5.50 × 10−5

^aCI = confidence interval; LoF = loss-of-function (deleterious) variants; NFE = non-Finnish European; RR = relative risk; UM = uveal melanoma; — = no value given here because the relative risk, confidence interval, and statistic tests are presented between the UM consecutive series and each GnomAD subpopulation in the rows below.

^bNFE population subset of the Genome Aggregation Database (GnomAD v2.1.1).

^cFor all GnomAD populations described, refers to the median number of allele count.

^dRR here is calculated by dividing the LoF frequency in the UM consecutive series by the LoF frequency in the corresponding GnomAD population subset.

^eConfidence interval of the relative risk is calculated as previously described (15).

^fSeven LoF variants correspond to the 8 deleterious MBD4 variants identified in this study, with removal of the missense deleterious variant p. Arg468Trp so as to restrict the analysis to LoF variants as defined by GnomAD for accurate comparison.