ClinVar Genomic variation as it relates to human health
NM_001379180.1(ESRRB):c.*1474T>C
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.
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.
Uncertain significance(2); Benign(2); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001379180.1(ESRRB):c.*1474T>C
Variation ID: 44997 Accession: VCV000044997.46
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 14q24.3 14: 76499932 (GRCh38) [ NCBI UCSC ] 14: 76966275 (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 Dec 6, 2016 Apr 15, 2024 Jan 22, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001379180.1:c.*1474T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NM_004452.4:c.1366T>C NP_004443.3:p.Phe456Leu missense NC_000014.9:g.76499932T>C NC_000014.8:g.76966275T>C NG_012278.2:g.133586T>C - Protein change
- F456L
- Other names
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- Canonical SPDI
- NC_000014.9:76499931:T: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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0.00339 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00318
1000 Genomes Project 30x 0.00328
1000 Genomes Project 0.00339
Exome Aggregation Consortium (ExAC) 0.00353
The Genome Aggregation Database (gnomAD) 0.00354
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00369
Trans-Omics for Precision Medicine (TOPMed) 0.00392
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 | ||
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HI score
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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. |
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ESRRB | - | - |
GRCh38 GRCh37 |
247 | 270 |
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. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jul 17, 2017 | RCV000038136.12 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Feb 3, 2022 | RCV000392529.13 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 22, 2024 | RCV000487923.25 |
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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Benign
(May 31, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000061802.5
First in ClinVar: May 03, 2013 Last updated: Dec 19, 2017 |
Comment:
Phe456Leu in Exon 10 of ESRRB: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (32/7020) of … (more)
Phe456Leu in Exon 10 of ESRRB: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (32/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project and in 0.5% (12/2178) of chromosomes by the 1000 Genome Project (http://evs.gs.washing ton.edu/EVS; dbSNP rs188462546). (less)
Number of individuals with the variant: 12
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Likely benign
(Feb 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 35
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002505977.2
First in ClinVar: May 07, 2022 Last updated: Dec 24, 2022 |
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Likely benign
(Jan 22, 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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Invitae
Accession: SCV001111414.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Uncertain significance
(Jul 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000618372.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Comment:
The F456L variant in the ESRRB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more)
The F456L variant in the ESRRB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The F456L variant is observed in 58/10360 (0.56%) alleles from individuals of Latino background and in 306/61610 (0.50%) alleles from individuals of non-Finnish European background including 2 homozygous individuals, in the ExAC dataset (Lek et al., 2016). The F456L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret F456L as a variant of uncertain significance. (less)
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Benign
(Jul 17, 2017)
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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: SCV000855414.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 35
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000388904.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Likely benign
(Jan 01, 2024)
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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: SCV000574983.26
First in ClinVar: May 08, 2017 Last updated: Apr 15, 2024 |
Comment:
ESRRB: BP4, BS2
Number of individuals with the variant: 3
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ESRRB | - | - | - | - |
Text-mined citations for rs188462546 ...
HelpRecord last updated Apr 15, 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.