NM_175914.5:c.1217-67C>G
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_175914.5(HNF4A):c.1217-67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,595,626 control chromosomes in the GnomAD database, including 279,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_175914.5 intron
Scores
Clinical Significance
Conservation
Publications
- maturity-onset diabetes of the young type 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
- monogenic diabetesInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- diabetes mellitus, noninsulin-dependentInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- Fanconi renotubular syndrome 4 with maturity-onset diabetes of the youngInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P
- hyperinsulinism due to HNF4A deficiencyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- maturity-onset diabetes of the youngInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.567 AC: 85607AN: 151020Hom.: 24597 Cov.: 28 show subpopulations
GnomAD4 exome AF: 0.591 AC: 853730AN: 1444488Hom.: 255323 AF XY: 0.593 AC XY: 426397AN XY: 719238 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.567 AC: 85635AN: 151138Hom.: 24593 Cov.: 28 AF XY: 0.563 AC XY: 41530AN XY: 73760 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:2
- -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Maturity onset diabetes mellitus in young Benign:1
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 rs3746575 in MODY, yet. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at