A wide range of resources exists to make predictions about the functional consequences of variants, as well as navigating groups of linked variants using LD information. Polyphen (7), SIFT (8) and SNPS3D (9) all make predictions of the impact of missense SNPs. Algorithms such as is-rSNP (10) and RAVEN (11) use regulatory motif changes to predict SNPs that may influence transcriptional regulation. SNPinfo (12) combines missense predictions with TRANSFAC PWM disruption predictions and conservation information across 17 vertebrates for HapMap Phase III SNPs. SNAP (13) provides LD calculations using 1000 Genomes Project pilot data with information about neighboring genes and array membership for proxy/tag SNP selection, but does not currently include indels. HaploReg improves on SNAP by providing LD calculation of 1000 Genomes Project pilot indels associated with query SNPs. In addition, the features of SNPinfo are improved upon by incorporating evolutionary constraint based on two alogrithms (involving the sequences of at least 29 mammals) and considering a much larger library of PWMs.
