dbNSFP: A Lightweight Database of Human Nonsynonymous SNPs and Their Functional Predictions

Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Human Mutation (Impact Factor: 5.14). 08/2011; 32(8):894-9. DOI: 10.1002/humu.21517
Source: PubMed


With the advance of sequencing technologies, whole exome sequencing has increasingly been used to identify mutations that cause human diseases, especially rare Mendelian diseases. Among the analysis steps, functional prediction (of being deleterious) plays an important role in filtering or prioritizing nonsynonymous SNP (NS) for further analysis. Unfortunately, different prediction algorithms use different information and each has its own strength and weakness. It has been suggested that investigators should use predictions from multiple algorithms instead of relying on a single one. However, querying predictions from different databases/Web-servers for different algorithms is both tedious and time consuming, especially when dealing with a huge number of NSs identified by exome sequencing. To facilitate the process, we developed dbNSFP (database for nonsynonymous SNPs' functional predictions). It compiles prediction scores from four new and popular algorithms (SIFT, Polyphen2, LRT, and MutationTaster), along with a conservation score (PhyloP) and other related information, for every potential NS in the human genome (a total of 75,931,005). It is the first integrated database of functional predictions from multiple algorithms for the comprehensive collection of human NSs. dbNSFP is freely available for download at

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Available from: Xiaoming Liu,
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    • "The variant is predicted to have a deleterious effect on protein function by bioinformatic analysis using SIFT and PolyPhen-2 (Table 2). Other prediction programs however give variable results [Liu et al., 2011] (Supp. Table S2). "
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    • "Only non-synonymous changes (SNPs and in-dels), those that cause an alternate splice site, and/or an aberrant stop codon, were considered for further analysis. For nonsynonymous changes, all insertion and deletion variants were considered damaging, whereas SNP variants were crossreferenced to the dbNSFP database to determine whether the changes to the protein structure would be considered tolerable or damaging using four algorithms (Sorting Intolerant From Tolerant (SIFT), PolyPhen2, likelihood ratio test [LRT], or MutationTaster) (Liu et al., 2011). Putative mutations identified were confirmed with traditional Sanger sequencing in both affected and unaffected family members (primers and conditions available upon request). "
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