Broader functional annotation of known as well as putative genetic variations is a valuable mean for prioritizing targets in disease studies and large-scale genotyping projects. In this article, we present a practical guide to SNPnexus, a web-based tool that provides an aggregate set of functional annotations for genomic variation data by characterizing related consequences at the transcriptome/proteome levels with in-depth analysis of potential deleterious effects, inferring physical and cytogenetic mapping, reporting related HapMap data, finding overlaps with potential regulatory, structural as well as conserved elements and retrieving links with previously reported genetic disease studies. We focus on the SNPnexus query system, its annotation categories and the biological interpretation of results. 