rs886056679
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM2_SupportingBP4
This summary comes from the ClinGen Evidence Repository: The c.50-4791_50-4788del variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, is a 4-nucleotide-deletion within intron 1 of NM_175914.5. The computational splicing predictor SpliceAI gives a score of 0.00 for donor and acceptor loss, suggesting that the variant has no impact on splicing (BP4). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.50-4791_50-4788del meets the criteria to be classified as VUS for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): BP4, PM2_Supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA10643872/MONDO:0015967/085
Frequency
Consequence
NM_000457.6 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151980Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000558 AC: 8AN: 1433744Hom.: 0 AF XY: 0.00000562 AC XY: 4AN XY: 711662
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151980Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74234
ClinVar
Submissions by phenotype
Maturity onset diabetes mellitus in young Uncertain:1Benign:1
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Potent mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. Associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, more evidence is required to ascertain the role of this particular variant rs886056679 in MODY, yet. -
Monogenic diabetes Uncertain:1
The c.50-4791_50-4788del variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, is a 4-nucleotide-deletion within intron 1 of NM_175914.5. The computational splicing predictor SpliceAI gives a score of 0.00 for donor and acceptor loss, suggesting that the variant has no impact on splicing (BP4). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.50-4791_50-4788del meets the criteria to be classified as VUS for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): BP4, PM2_Supporting. -
Hyperinsulinism, Dominant Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at