rs121918671
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000458.4(HNF1B):c.301G>T(p.Glu101Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
HNF1B
NM_000458.4 stop_gained
NM_000458.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
HNF1B (HGNC:11630): (HNF1 homeobox B) This gene encodes a member of the homeodomain-containing superfamily of transcription factors. The protein binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-37744584-C-A is Pathogenic according to our data. Variant chr17-37744584-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 12638.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-37744584-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF1B | NM_000458.4 | c.301G>T | p.Glu101Ter | stop_gained | 1/9 | ENST00000617811.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF1B | ENST00000617811.5 | c.301G>T | p.Glu101Ter | stop_gained | 1/9 | 1 | NM_000458.4 | ||
HNF1B | ENST00000621123.4 | c.301G>T | p.Glu101Ter | stop_gained | 1/9 | 1 | P1 | ||
HNF1B | ENST00000613727.4 | c.301G>T | p.Glu101Ter | stop_gained | 1/7 | 1 | |||
HNF1B | ENST00000614313.4 | c.301G>T | p.Glu101Ter | stop_gained | 1/8 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Renal cysts and diabetes syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | literature only | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Jul 06, 2019 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2001 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at