Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 23;37(8):1171-1173.
doi: 10.1093/bioinformatics/btaa783.

Annotating high-impact 5'untranslated region variants with the UTRannotator

Xiaolei Zhang  1   2 , Matthew Wakeling  3 , James Ware  1   2 , Nicola Whiffin  1   2
Affiliations

Annotating high-impact 5'untranslated region variants with the UTRannotator

Xiaolei Zhang et al. Bioinformatics. .

Abstract

Summary: Current tools to annotate the predicted effect of genetic variants are heavily biased towards protein-coding sequence. Variants outside of these regions may have a large impact on protein expression and/or structure and can lead to disease, but this effect can be challenging to predict. Consequently, these variants are poorly annotated using standard tools. We have developed a plugin to the Ensembl Variant Effect Predictor, the UTRannotator, that annotates variants in 5'untranslated regions (5'UTR) that create or disrupt upstream open reading frames. We investigate the utility of this tool using the ClinVar database, providing an annotation for 31.9% of all 5'UTR (likely) pathogenic variants, and highlighting 31 variants of uncertain significance as candidates for further follow-up. We will continue to update the UTRannotator as we gain new knowledge on the impact of variants in UTRs.

Availability and implementation: UTRannotator is freely available on Github: https://github.com/ImperialCardioGenetics/UTRannotator.

Supplementary information: Supplementary data are available at Bioinformatics online.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
5′UTR variants in ClinVar annotated by the UTRannotator. (a) A schematic showing the five distinct consequences of 5′UTR variants annotated by the tool: those that create an upstream AUG (uAUG_gained), those that disrupt the start site of an existing upstream open reading frame (uORF; uAUG_lost), those that cause a frameshift in the sequence of the uORF (uFrameShift), those that introduce a new stop codon into an existing uORF (uSTOP_gained) and those that disrupt the stop site of an existing uORF (uSTOP_lost). (b) The counts of each variant category that are classified as Pathogenic/Likely Pathogenic (teal) or Uncertain Significance (VUS; grey) in ClinVar
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aïssi D. et al. (2020) MORFEE: a new tool for detecting and annotating single nucleotide variants creating premature ATG codons from VCF files. bioRxiv, 2020.03.29.012054.
    1. Calvo S.E. et al. (2009) Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proc. Natl. Acad. Sci. USA, 106, 7507–7512. - PMC - PubMed
    1. Kozak M. (1989) The scanning model for translation: an update. J. Cell Biol., 108, 229–241. - PMC - PubMed
    1. Landrum M.J. et al. (2018) ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res., 46, D1062–D1067. - PMC - PubMed
    1. McGillivray P. et al. (2018) A comprehensive catalog of predicted functional upstream open reading frames in humans. Nucleic Acids Res., 46, 3326–3338. - PMC - PubMed

Publication types

Substances