rs201039488
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_000545.8(HNF1A):c.1309+184dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,506,614 control chromosomes in the GnomAD database, including 58 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0052 ( 18 hom., cov: 31)
Exomes 𝑓: 0.0044 ( 40 hom. )
Consequence
HNF1A
NM_000545.8 intron
NM_000545.8 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.992
Genes affected
HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
?
Variant 12-120996922-C-CA is Benign according to our data. Variant chr12-120996922-C-CA is described in ClinVar as [Benign]. Clinvar id is 135500.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 797 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1309+184dup | intron_variant | ENST00000257555.11 | |||
HNF1A | NM_001306179.2 | c.1309+184dup | intron_variant | ||||
HNF1A | NM_001406915.1 | c.1309+184dup | intron_variant | ||||
HNF1A | XM_024449168.2 | c.1309+184dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1309+184dup | intron_variant | 1 | NM_000545.8 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00525 AC: 797AN: 151846Hom.: 18 Cov.: 31
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GnomAD3 exomes AF: 0.00573 AC: 843AN: 147196Hom.: 11 AF XY: 0.00523 AC XY: 415AN XY: 79328
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GnomAD4 exome AF: 0.00441 AC: 5968AN: 1354650Hom.: 40 Cov.: 23 AF XY: 0.00434 AC XY: 2910AN XY: 670342
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GnomAD4 genome ? AF: 0.00524 AC: 797AN: 151964Hom.: 18 Cov.: 31 AF XY: 0.00626 AC XY: 465AN XY: 74274
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Maturity onset diabetes mellitus in young Benign:1
Benign, 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 cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs201039488 with MODY3. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at