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 dataSupplementary data are available at Bioinformatics online.

中文翻译：

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使用 UTrannotator 注释高影响 5' 非翻译区变体

摘要

概括

当前注释遗传变异的预测效果的工具严重偏向于蛋白质编码序列。这些区域之外的变异可能对蛋白质表达和/或结构产生很大影响，并可能导致疾病，但这种影响可能难以预测。因此，使用标准工具对这些变体进行不良注释。我们为 Ensembl Variant Effect Predictor 开发了一个插件，即 UTRannotator，它注释 5' 非翻译区域 (5' UTR) 中的变体，这些区域创建或破坏上游开放阅读框。我们使用 ClinVar 数据库调查该工具的实用性，为所有 5 '中的 31.9% 提供注释UTR（可能）致病变异，并突出显示 31 个意义不确定的变异作为进一步随访的候选者。随着我们获得有关 UTR 中变体影响的新知识，我们将继续更新 UTRannotator。

可用性和实施

UTRannotator 在 Github 上免费提供：https://github.com/ImperialCardioGenetics/UTRannotator。

补充资料

补充数据补充数据可在生物信息学在线获得。