NM_001379180.1(ESRRB):c.*1474T>C AND not specified

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jul 17, 2017
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000038136.12

Allele description [Variation Report for NM_001379180.1(ESRRB):c.*1474T>C]

NM_001379180.1(ESRRB):c.*1474T>C

Gene:

ESRRB:estrogen related receptor beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.3

Genomic location:

Preferred name:

NM_001379180.1(ESRRB):c.*1474T>C

HGVS:

NC_000014.9:g.76499932T>C
NG_012278.2:g.133586T>C
NM_001379180.1:c.*1474T>CMANE SELECT
NM_004452.4:c.1366T>C
NP_004443.3:p.Phe456Leu
NP_004443.3:p.Phe456Leu
NC_000014.8:g.76966275T>C
NM_004452.3:c.1366T>C
c.1366T>C

Protein change:

F456L

Links:

dbSNP: rs188462546

NCBI 1000 Genomes Browser:

rs188462546

Molecular consequence:

NM_001379180.1:c.*1474T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_004452.4:c.1366T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000061802	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (May 31, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000618372	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Jul 7, 2017)	germline	clinical testing	Citation Link,
SCV000855414	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Jul 17, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061802

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Benign
(May 31, 2013)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000618372

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Jul 7, 2017)

germline

clinical testing

Citation Link,

SCV000855414

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Benign
(Jul 17, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	12	12	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061802.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	12	not provided	not provided	clinical testing	PubMed (1)

Description

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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		12	not provided	12	not provided

From GeneDx, SCV000618372.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000855414.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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