rs2464196
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000545.8(HNF1A):c.1460G>A(p.Ser487Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,612,298 control chromosomes in the GnomAD database, including 80,461 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.
Frequency
Consequence
NM_000545.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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HNF1A | NM_000545.8 | c.1460G>A | p.Ser487Asn | missense_variant | Exon 7 of 10 | ENST00000257555.11 | NP_000536.6 | |
HNF1A | NM_001306179.2 | c.1460G>A | p.Ser487Asn | missense_variant | Exon 7 of 10 | NP_001293108.2 | ||
HNF1A | XM_024449168.2 | c.1460G>A | p.Ser487Asn | missense_variant | Exon 7 of 9 | XP_024304936.1 | ||
HNF1A | NM_001406915.1 | c.1309+882G>A | intron_variant | Intron 6 of 8 | NP_001393844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1460G>A | p.Ser487Asn | missense_variant | Exon 7 of 10 | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes AF: 0.273 AC: 41508AN: 152026Hom.: 6414 Cov.: 32
GnomAD3 exomes AF: 0.337 AC: 83546AN: 247590Hom.: 14870 AF XY: 0.343 AC XY: 45944AN XY: 134104
GnomAD4 exome AF: 0.312 AC: 456021AN: 1460154Hom.: 74045 Cov.: 42 AF XY: 0.316 AC XY: 229707AN XY: 726350
GnomAD4 genome AF: 0.273 AC: 41510AN: 152144Hom.: 6416 Cov.: 32 AF XY: 0.280 AC XY: 20838AN XY: 74374
ClinVar
Submissions by phenotype
not specified Benign:6Other:1
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. -
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. -
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not provided Benign:3
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Maturity-onset diabetes of the young type 3 Benign:3
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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. -
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Type 2 diabetes mellitus Benign:1
rs2464196 of HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria and may respond to sulfonylureas. -
Maturity onset diabetes mellitus in young Benign:1
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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at