Next-generation DNA sequencing has recently empowered scientists to identify genetic variations associated with human disease at higher resolution and greater sensitivity than previously possible. Our HumanVariome project goes beyond other projects in both sequencing depth of the sequencing and size of the cohort analysed at high depth. We have utilized the latest Oracle 11i technology, which is centered on a database model designed to store genomic variations and annotations detected using the Complete Genomics (CG) sequencing3 platform. Currently, the database contains almost 100 genomes from Erasmus MC and V.I.B of which a subset, 41 genomes (“Unaffected” cohort), have been used initially. The application has been developed to be file format independent, to allow for enriched variation reporting and includes additional 60 genomes, made publicly by CG. The total content of the HumanVariome project comprises 248 Gb, 202 Gb and 246 Gb of mapped reads for “Affected”, “Unaffected” and “Normal Tissues from Cancer Patients” cohorts, respectively, representing an average of > 80x coverage for the three groups. In total, nearly 1 million novel SNVs have been identified for the “Unaffected” cohort (70% have complete calling of both alleles). In summary, we present a resource for prioritizing rare SNVs identified with NGS technology. In contrast with other projects, only high coverage genome sequences are used and no imputation has been used to infer unsequenced variants. In addition, our resource has successfully been used to prioritize candidate cancer targets and genomic variations detected in familial congenital malformations. ; status: submitted