Integrating 400 million variants from 80,000 human samples with extensive annotations: towards a knowledge base to analyze disease cohorts

Table 4 Variants in clinical annotation databases observed in healthy cohorts, binned by maximum ethnicity-specific allele frequency across cohorts. Bins are non-cumulative and intervals exclude the value of the upper boundary

Source	0	0–0.001	0.001–0.005	0.005–0.01	0.01–0.05	0.05–0.1	0.1–0.5	≥0.5	Total
ClinVar: pathogenic	30.09	2.59	0.86	0.20	0.26	0.05	0.14	0.02	34.21
ClinVar: likely pathogenic	3.26	0.29	0.08	0.01	0.02				3.66
ClinVar: risk factor	0.35	0.03	0.06	0.02	0.05	0.02	0.13	0.10	0.76
ClinVar: association	0.01	<0.01	<0.01	0.01	0.01	<0.01	0.05	0.02	0.10
ClinVar: likely benign	0.47	0.95	1.01	0.49	0.51	0.05	0.05	0.01	3.54
ClinVar: benign	0.49	0.26	0.47	0.62	2.33	1.10	2.61	1.70	9.58
ClinVar: protective	<0.01		<0.01			<0.01	0.02	0.01	0.03
ClinVar: drug response	<0.01				<0.01		0.01	0.01	0.02
ClinVar: uncertain significance	8.15	2.05	1.53	0.37	0.36	0.05	0.06	0.03	12.60
ClinVar: other	1.02	0.05	0.04	0.02	0.03	0.01	0.15	0.08	1.40
ClinVar: unknown	29.44	2.58	0.97	0.19	0.38	0.12	0.31	0.11	34.10
HGMD: DM	81.24	4.17	1.40	0.39	0.46	0.05	0.04	0.01	87.76
HGMD: DM?	4.80	0.61	0.50	0.17	0.35	0.12	0.17	0.02	6.74
HGMD: DFP	0.16	0.01	0.02	0.01	0.07	0.08	0.48	0.29	1.12
HGMD: DP	0.30	0.03	0.06	0.04	0.13	0.09	0.71	0.45	1.81
HGMD: FP	0.86	0.15	0.16	0.09	0.20	0.09	0.32	0.15	2.02
HGMD: FTV	0.32	0.06	0.03	0.01	0.03	0.01	0.04	0.03	0.53
OMIM: pathogenic	72.24	8.69	3.19	1.00	1.14	0.26	0.73	0.23	87.48
OMIM: probably pathogenic	0.02								0.02
OMIM: probably not pathogenic			0.01						0.01
OMIM: risk factor	1.33	0.23	0.28	0.06	0.29	0.13	0.59	0.57	3.48
OMIM: association	0.02	0.01		0.01		0.01	0.06	0.09	0.20
OMIM: no known pathogenicity	0.11	0.03	0.04	0.03	0.11	0.06	0.39	0.15	0.92
OMIM: confers sensitivity							0.01		0.01
OMIM: protective	0.01		0.01			0.03	0.06	0.05	0.16
OMIM: drug response		0.01			0.02		0.05	0.07	0.15
OMIM: other	6.46	0.32	0.15	0.06	0.03	0.03	0.04	0.01	7.10
OMIM: VUS	0.11	0.08	0.07	0.03	0.03	0.05	0.09	0.05	0.51

Values represent the percentage of variants from the respective resource that fall into each category and bin. DM, disease-causing mutation; DM?, likely DM; DP, disease-associated polymorphism; DFP, DP with additional functional evidence; FP, functional polymorphism; FTV, frameshift or truncating; VUS, variant of unknown significance

ISSN: 1471-2105