Variant chr14-76491544-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379180.1(ESRRB):c.948T>C(p.Tyr316=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,595,430 control chromosomes in the GnomAD database, including 796,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75520 hom., cov: 38)

Exomes 𝑓: 1.0 ( 720783 hom. )

Consequence

ESRRB
NM_001379180.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.79

Variant links:

Genes affected

ESRRB (HGNC:3473): (estrogen related receptor beta) This gene encodes a protein with similarity to the estrogen receptor. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development. [provided by RefSeq, Jul 2008]

ESRRB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-76491544-T-C is Benign according to our data. Variant chr14-76491544-T-C is described in ClinVar as [Benign]. Clinvar id is 45002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-76491544-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESRRB	NM_001379180.1 linkuse as main transcript	c.948T>C	p.Tyr316=	synonymous_variant	6/7	ENST00000644823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRRB	ENST00000644823.1 linkuse as main transcript	c.948T>C	p.Tyr316=	synonymous_variant	6/7		NM_001379180.1	P1

Frequencies

GnomAD3 genomes

AF:

0.996

AC:

151604

AN:

152270

Hom.:

75473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.985

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.997

GnomAD3 exomes

AF:

0.999

AC:

221338

AN:

221584

Hom.:

110546

AF XY:

0.999

AC XY:

118971

AN XY:

119058

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

0.999

AC:

1442301

AN:

1443042

Hom.:

720783

Cov.:

AF XY:

1.00

AC XY:

715508

AN XY:

715824

show subpopulations

Gnomad4 AFR exome

AF:

0.985

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.999

GnomAD4 genome

AF:

0.996

AC:

151710

AN:

152388

Hom.:

75520

Cov.:

AF XY:

0.996

AC XY:

74183

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.985

Gnomad4 AMR

AF:

0.998

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.997

Alfa

AF:

0.998

Hom.:

32803

Bravo

AF:

0.995

Asia WGS

AF:

0.999

AC:

3473

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Tyr295Tyr in Exon 08 of ESRRB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 1.1% (42/3736) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2361293). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -

Autosomal recessive nonsyndromic hearing loss 35

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.18

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over