rs1169294
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000545.8(HNF1A):c.327-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,595,190 control chromosomes in the GnomAD database, including 86,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.29 ( 7146 hom., cov: 33)
Exomes 𝑓: 0.33 ( 78905 hom. )
Consequence
HNF1A
NM_000545.8 intron
NM_000545.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.273
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 12-120988791-G-A is Benign according to our data. Variant chr12-120988791-G-A is described in ClinVar as [Benign]. Clinvar id is 673535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120988791-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.327-42G>A | intron_variant | ENST00000257555.11 | |||
HNF1A | NM_001306179.2 | c.327-42G>A | intron_variant | ||||
HNF1A | NM_001406915.1 | c.327-42G>A | intron_variant | ||||
HNF1A | XM_024449168.2 | c.327-42G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.327-42G>A | intron_variant | 1 | NM_000545.8 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.294 AC: 44742AN: 152044Hom.: 7145 Cov.: 33
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GnomAD3 exomes AF: 0.348 AC: 84443AN: 242538Hom.: 15053 AF XY: 0.353 AC XY: 46269AN XY: 131146
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GnomAD4 exome AF: 0.327 AC: 471715AN: 1443028Hom.: 78905 Cov.: 30 AF XY: 0.330 AC XY: 237293AN XY: 718632
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GnomAD4 genome ? AF: 0.294 AC: 44744AN: 152162Hom.: 7146 Cov.: 33 AF XY: 0.302 AC XY: 22486AN XY: 74382
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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 rs1169294 with MODY3. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at