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.
ClinVar Genomic variation as it relates to human health
NM_000458.4(HNF1B):c.182T>G (p.Val61Gly)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(10)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(2); Likely benign(5)
Uncertain significance(1); Benign(2); Likely benign(5)
10
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000458.4(HNF1B):c.182T>G (p.Val61Gly)
Variation ID: 381601 Accession: VCV000381601.52
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q12 17: 37744703 (GRCh38) [ NCBI UCSC ] 17: 36104694 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 8, 2017 Oct 20, 2024 Feb 1, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000458.4:c.182T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000449.1:p.Val61Gly missense NM_001165923.4:c.182T>G NP_001159395.1:p.Val61Gly missense NM_001304286.2:c.182T>G NP_001291215.1:p.Val61Gly missense NC_000017.11:g.37744703A>C NC_000017.10:g.36104694A>C NG_013019.2:g.5404T>G - Protein change
- V61G
- Other names
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- Canonical SPDI
- NC_000017.11:37744702:A:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| HNF1B | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
638 | 855 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Dec 22, 2016 | RCV000440404.5 | |
| Likely benign (1) |
criteria provided, single submitter
|
Feb 15, 2019 | RCV000664148.3 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Jul 6, 2019 | RCV001127842.9 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV002062432.16 | |
| Likely benign (1) |
no assertion criteria provided
|
Sep 1, 2021 | RCV001844831.1 | |
| Likely benign (1) |
criteria provided, single submitter
|
Dec 1, 2023 | RCV004022349.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Mar 04, 2016)
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criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000521048.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
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 … (more)
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. (less)
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Likely benign
(Dec 22, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000703960.2
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Jul 06, 2019)
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criteria provided, single submitter
Method: literature only
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Renal cysts and diabetes syndrome
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
Accession: SCV000926180.1
First in ClinVar: Jul 14, 2019 Last updated: Jul 14, 2019
Comment:
This variant and it's classification has been reported by Vasileiou et al. 2019; DOI:10.1101/576918. The variants has previously been reported in PMID:25700310; PMID:15930087; PMID:18065799; PMID:30259503; … (more)
This variant and it's classification has been reported by Vasileiou et al. 2019; DOI:10.1101/576918. The variants has previously been reported in PMID:25700310; PMID:15930087; PMID:18065799; PMID:30259503; PMID:25536396; PMID:20633866; PMID:16249435 as "c.182T>G, c.376T>G; c.182T>G p.Val61Gly; c.182T>G; V61G/N p.Val61Gly" with clinical significance Pathogenic. It has been re-classified using InterVar and manual curation as Uncertain significance based on PM1 PP3 PP5 BP6. (less)
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Benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Renal cysts and diabetes syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001287192.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Likely benign
(Feb 15, 2019)
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criteria provided, single submitter
Method: research
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Monogenic diabetes
Affected status: unknown
Allele origin:
unknown
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Personalized Diabetes Medicine Program, University of Maryland School of Medicine
Accession: SCV000787600.2
First in ClinVar: Jul 21, 2018 Last updated: Jun 13, 2020 |
Comment:
ACMG criteria: PP3 (7 predictors), BP4 (2 predictors), BS2 (6 controls and 11 cases in T2DM and 2 homozygotes in ExAC) NOTE: GeneDx calls likely … (more)
ACMG criteria: PP3 (7 predictors), BP4 (2 predictors), BS2 (6 controls and 11 cases in T2DM and 2 homozygotes in ExAC) NOTE: GeneDx calls likely benign=Likely Benign (less)
Number of individuals with the variant: 1
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002405253.3
First in ClinVar: Apr 08, 2022 Last updated: Feb 14, 2024 |
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Likely benign
(Dec 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Maturity onset diabetes mellitus in young
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV005035557.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(Oct 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004144498.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Comment:
HNF1B: BS2
Number of individuals with the variant: 3
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Likely benign
(Sep 01, 2021)
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no assertion criteria provided
Method: research
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Autosomal dominant polycystic liver disease
Affected status: yes
Allele origin:
germline
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Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center
Accession: SCV001877062.1
First in ClinVar: Mar 19, 2022 Last updated: Mar 19, 2022 |
Sex: female
Geographic origin: Netherlands
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Likely benign
(Sep 07, 2022)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV003839585.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
|
Comment:
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Comment:
ACMG criteria: PP3 (7 predictors), BP4 (2 predictors), BS2 (6 controls and 11 cases in T2DM and 2 homozygotes in ExAC) NOTE: GeneDx calls likely benign=Likely Benign
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
HNF1B: BS2
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Comment:
ACMG criteria: PP3 (7 predictors), BP4 (2 predictors), BS2 (6 controls and 11 cases in T2DM and 2 homozygotes in ExAC) NOTE: GeneDx calls likely benign=Likely Benign
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
HNF1B: BS2
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young. | Komazec J | Endokrynologia Polska | 2019 | PMID: 30259503 |
| A novel mutation of the HNF1B gene associated with hypoplastic glomerulocystic kidney disease and neonatal renal failure: a case report and mutation update. | Alvelos MI | Medicine | 2015 | PMID: 25700310 |
| HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. | Clissold RL | Nature reviews. Nephrology | 2015 | PMID: 25536396 |
| Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract. | Hwang DY | Kidney international | 2014 | PMID: 24429398 |
| Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through one-step PCR-based enrichment in combination with next-generation sequencing. | Bonnefond A | Diabetes care | 2014 | PMID: 24041679 |
| Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes. | Flannick J | Nature genetics | 2013 | PMID: 24097065 |
| Genetic basis of prune belly syndrome: screening for HNF1β gene. | Granberg CF | The Journal of urology | 2012 | PMID: 22114815 |
| Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood. | Faguer S | Kidney international | 2011 | PMID: 21775974 |
| Mutations in the hepatocyte nuclear factor-1β (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations. | Oram RA | American journal of obstetrics and gynecology | 2010 | PMID: 20633866 |
| Missense mutations in EYA1 and TCF2 are a rare cause of urinary tract malformations. | Hoskins BE | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | 2008 | PMID: 18065799 |
| Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. | Edghill EL | Journal of medical genetics | 2006 | PMID: 15930087 |
| Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5. | Bellanné-Chantelot C | Diabetes | 2005 | PMID: 16249435 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HNF1B | - | - | - | - |
| type2diabetesgenetics.org | - | - | - | - |
| - | - | - | - | DOI: 10.1101/576918 |
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Text-mined citations for this variant ...
HelpRecord last updated Oct 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.