RegulationSpotter: annotation and interpretation of extratranscriptic DNA variants

Abstract

RegulationSpotter is a web-based tool for the user-friendly annotation and interpretation of DNA variants located outside of protein-coding transcripts (extratranscriptic variants). It is designed for clinicians and researchers who wish to assess the potential impact of the considerable number of non-coding variants found in Whole Genome Sequencing runs. It annotates individual variants with underlying regulatory features in an intuitive way by assessing over 100 genome-wide annotations. Additionally, it calculates a score, which reflects the regulatory potential of the variant region. Its dichotomous classifications, ‘functional’ or ‘non-functional’, and a human-readable presentation of the underlying evidence allow a biologically meaningful interpretation of the score. The output shows key aspects of every variant and allows rapid access to more detailed information about its possible role in gene regulation. RegulationSpotter can either analyse single variants or complete VCF files. Variants located within protein-coding transcripts are automatically assessed by MutationTaster as well as by RegulationSpotter to account for possible intragenic regulatory effects. RegulationSpotter offers the possibility of using phenotypic data to focus on known disease genes or genomic elements interacting with them. RegulationSpotter is freely available at https://www.regulationspotter.org.

MutationTaster2021

“…Variants within RNA genes or outwith genes cannot be assessed. Although we offer some prediction functions for such variants in our tool RegulationSpotter ( 24 ), we should state that we do not consider predictions for extragenic variants as reliable enough to be included in MutationTaster.…”

Bone density and genomic analysis unfold cold adaptation mechanisms of ancient inhabitants of Tierra del Fuego

“…Candidate variants were further characterized based on possible functional effect as predicted by in silico analysis using MutationTaster 55 and RegulationSpotter 56 .These are online applications performing several in silico tests on both DNA and protein level ultimately estimating the impact of the identified variant, such as functional consequences of synonymous or intronic mutations up to amino acid substitutions, deletion and insertion of sequences, or variants within the intron–exon border.…”

Novel variations in spermatogenic transcription regulators RFX2 and TAF7 increase risk of azoospermia

“…To predict the probable damaging effect of the genetic variants, several in silico methods were applied. These include PROVEAN (Protein Variation Effect Analyzer) [16], predicting impact of amino acid substitution or indel on the biological function of a protein, PolyPhen-2 (Polymorphism Phenotyping v2) [17] for predicting possible impact of an amino acid substitution on the structure and function of protein, Mutation t@ster, [18] for analysing the diseasecausing potential of DNA variants, Regulation Spotter [19] to annotate of extratranscriptic variant, SIFT(Sorting Intolerant From Tolerant) [20], for analysing effect of amino acid substitution on protein function as functionally neutral or deleterious. Moreover, Human Splice Finder [21] and SpliceAid [22] was used to predict any change in transcript structure that imperils potential splice sites owing to polymorphic variations or mutations.. A deleterious effects of mutation or variation on protein structure was developed by Robetta [23] server (http:// robet ta.…”