12-120996929-T-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_000545.8(HNF1A):c.1309+187T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,501,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000069 ( 0 hom. )
Consequence
HNF1A
NM_000545.8 intron
NM_000545.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.184
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 12-120996929-T-A is Benign according to our data. Variant chr12-120996929-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 135501.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 62 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1309+187T>A | intron_variant | ENST00000257555.11 | NP_000536.6 | |||
HNF1A | NM_001306179.2 | c.1309+187T>A | intron_variant | NP_001293108.2 | ||||
HNF1A | NM_001406915.1 | c.1309+187T>A | intron_variant | NP_001393844.1 | ||||
HNF1A | XM_024449168.2 | c.1309+187T>A | intron_variant | XP_024304936.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1309+187T>A | intron_variant | 1 | NM_000545.8 | ENSP00000257555.5 |
Frequencies
GnomAD3 genomes AF: 0.000415 AC: 63AN: 151798Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000116 AC: 17AN: 147080Hom.: 0 AF XY: 0.000114 AC XY: 9AN XY: 79282
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GnomAD4 exome AF: 0.0000689 AC: 93AN: 1349536Hom.: 0 Cov.: 22 AF XY: 0.0000599 AC XY: 40AN XY: 668156
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GnomAD4 genome AF: 0.000408 AC: 62AN: 151916Hom.: 0 Cov.: 31 AF XY: 0.000377 AC XY: 28AN XY: 74228
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Maturity onset diabetes mellitus in young Benign:1
Likely 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 rs184963118 with MODY3. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at