# Frequency of variants of unknown significance by ancestry groups in the All of Us Research Program cohort

> **NIH NIH U01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $119,939

## Abstract

PROJECT SUMMARY
Variants of uncertain significance (VUS) pose many problems in the delivery of genomic medicine, as they are
hard to interpret for clinicians and confusing for patients. One important piece of evidence that can be used to
reclassify VUS is case/control data; an enrichment of a particular variant in patients with a specific disease
(generally already known to be related to the gene in which the variant occurs) is strong evidence for
pathogenicity of that variant. The All of Us research program is assembling a cohort with unprecedented
diversity that combines genetic data with electronic health records (EHR). This creates the opportunity to
examine many VUS that have never been seen before, and explore the utility of the EHR data to build sets of
AoU participants that fall into case and control groups. This project will thus inform variant classification, but
also create a toolset for the researcher workbench that is currently missing: the ability to sift through and
prioritize clinically-relevant variants. Additionally, data collected in this study will likely bear on health
disparities. Previous studies have shown that pathogenic variants are distributed differently among groups with
different ancestry backgrounds. The same is likely to be true for VUS, especially in understudied populations.
Collecting data on VUS prevalence will allow the targeting of future efforts aimed at reducing these disparities.

## Key facts

- **NIH application ID:** 10659798
- **Project number:** 3U01HG011758-02S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** RICHARD A GIBBS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $119,939
- **Award type:** 3
- **Project period:** 2021-07-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10659798

## Citation

> US National Institutes of Health, RePORTER application 10659798, Frequency of variants of unknown significance by ancestry groups in the All of Us Research Program cohort (3U01HG011758-02S1). Retrieved via AI Analytics 2026-06-07 from https://api.ai-analytics.org/grant/nih/10659798. Licensed CC0.

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