rs2464195
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_000545.8(HNF1A):c.1501+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,601,934 control chromosomes in the GnomAD database, including 110,205 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000545.8 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1501+7G>A | splice_region_variant, intron_variant | ENST00000257555.11 | |||
HNF1A | NM_001306179.2 | c.1501+7G>A | splice_region_variant, intron_variant | ||||
HNF1A | NM_001406915.1 | c.1309+930G>A | intron_variant | ||||
HNF1A | XM_024449168.2 | c.1501+7G>A | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1501+7G>A | splice_region_variant, intron_variant | 1 | NM_000545.8 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.318 AC: 48276AN: 152006Hom.: 8635 Cov.: 33
GnomAD3 exomes AF: 0.390 AC: 90608AN: 232434Hom.: 18320 AF XY: 0.401 AC XY: 50497AN XY: 126044
GnomAD4 exome AF: 0.368 AC: 533834AN: 1449810Hom.: 101568 Cov.: 34 AF XY: 0.374 AC XY: 269555AN XY: 720574
GnomAD4 genome ? AF: 0.317 AC: 48277AN: 152124Hom.: 8637 Cov.: 33 AF XY: 0.326 AC XY: 24281AN XY: 74370
ClinVar
Submissions by phenotype
not specified Benign:3Other:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 22, 2013 | 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. - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 12, 2017 | - - |
Maturity-onset diabetes of the young type 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Type 2 diabetes mellitus Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially multiple cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, no sufficient evidence is found to support association of rs2464195 with T2DM or MODY. - |
Maturity onset diabetes mellitus in young Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Nonpapillary renal cell carcinoma Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at