rs1169304
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000257555.11(HNF1A):c.1623+29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,613,794 control chromosomes in the GnomAD database, including 531,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.76 ( 44840 hom., cov: 32)
Exomes 𝑓: 0.81 ( 486392 hom. )
Consequence
HNF1A
ENST00000257555.11 intron
ENST00000257555.11 intron
Scores
1
14
Clinical Significance
Conservation
PhyloP100: -3.77
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 (MetaRNN=8.387669E-7).
BP6
Variant 12-120999418-T-C is Benign according to our data. Variant chr12-120999418-T-C is described in ClinVar as [Benign]. Clinvar id is 135505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120999418-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HNF1A | NM_000545.8 | c.1623+29T>C | intron_variant | ENST00000257555.11 | NP_000536.6 | |||
HNF1A | XM_024449168.2 | c.1652T>C | p.Leu551Ser | missense_variant | 8/9 | XP_024304936.1 | ||
HNF1A | NM_001306179.2 | c.1623+29T>C | intron_variant | NP_001293108.2 | ||||
HNF1A | NM_001406915.1 | c.1431+29T>C | intron_variant | NP_001393844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HNF1A | ENST00000257555.11 | c.1623+29T>C | intron_variant | 1 | NM_000545.8 | ENSP00000257555 | P4 |
Frequencies
GnomAD3 genomes AF: 0.759 AC: 115468AN: 152032Hom.: 44808 Cov.: 32
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GnomAD3 exomes AF: 0.823 AC: 206387AN: 250922Hom.: 85692 AF XY: 0.824 AC XY: 111903AN XY: 135758
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GnomAD4 exome AF: 0.814 AC: 1190214AN: 1461644Hom.: 486392 Cov.: 86 AF XY: 0.815 AC XY: 592744AN XY: 727132
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GnomAD4 genome AF: 0.759 AC: 115548AN: 152150Hom.: 44840 Cov.: 32 AF XY: 0.763 AC XY: 56764AN XY: 74372
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3148
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ClinVar
Significance: Benign
Submissions summary: Benign:4Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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. Sufficient evidence is found to confer the association of this particular variant rs1169304 with MODY3. - |
Maturity-onset diabetes of the young type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
D
Sift4G
Benign
T
Vest4
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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