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

Table 1 Number of variants imported from various external resources

Study	Variant sites	Variants	Unique to study	Variants passed	Samples
1000 Genomes [1]	81,195,126	81,693,252	57,400,612	all	2,504
ESP6500 [2]	1,982,177	1,998,204	184,225	all	6,503
UK10K [47] ALSPAC/TWINS	37,258,978	37,560,436	6,155,493	all	2,432
UK10K with disease ^c	9,391,582	11,177,227	8,847,466	9,969,036	4,888
TCGA [4] germline ^c	200,691,728	219,533,884	90,884,769	n/a	4,224
TCGA somatic	876,970	890,172	696,754	all	4,205
Scripps Wellderly [48]	76,144,271	91,947,469	63,331,143	53,303,437	534
ExAC ^b [3]	9,579,712	10,450,724	6,581,946	8,811,372	63,352
MSSM BioBank genotyping	849,806	849,806	0	all	11,210
In-house resequencing study	29,326,393	29,671,729	10,134,258	23,610,572	142
Total observed	358,152,122	399,404,510	244,216,666	>217,796,115	82,558 ^b
Other resources:
dbNSFP ^a [18]	30,523,109	89,617,785	73,561,239	—	—
ClinVar [12]	101,317	104,455	31,694	—	—
OMIM [49]	10,863	10,913	—	—	—
COSMIC [50]	1,483,983	1,525,243	—	—	—
PharmGKB ^c [51]	672	684	—	—	—
SwissVar ^d	(77,047)	(84,649)	(34,198)	—	—
HGMD ^c [13]	125,744	133,464	32,178	—	—
Literature mining	—	890,665	—	—	—
Total observed + other	388,902,292	472,965,749	317,841,777	>217,796,115	82,558

The first block refers to sequencing/genotyping studies, the second to sample-independent annotation databases. “Unique to study” counts variants that were observed only in that particular study. “Variants passed” refers to variants that passed quality metrics as defined by the particular study, at least one sample has to pass; n/a: individual sample quality metrics not available. Totals exclude duplicates seen in different studies. Variants in annotation databases are included only if they can be mapped to precise coordinates and allele. Since a large proportion of the variants discovered by literature mining are given at the protein level only, they were not compared to other studies
^adbNSFP contains hypothetical variants, see text
^bExAC includes samples from 1000 Genomes, ESP6500, and TCGA
^cNote that data from HGMD, PharmGKB, UK10K diseases and TCGA germline are not visible to external users on the RVS website
^dCounts for SwissVar refer to distinct amino acid changes. Further details on individual resources are provided in Additional file 4: Table S3

ISSN: 1471-2105