rs146351534

Positions:

chr14-76498393-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001379180.1(ESRRB):c.1300G>A(p.Val434Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,613,450 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 14 hom., cov: 32)

Exomes 𝑓: 0.013 ( 187 hom. )

Consequence

ESRRB
NM_001379180.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.85

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007202655).

BP6

Variant 14-76498393-G-A is Benign according to our data. Variant chr14-76498393-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 44996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0107 (1637/152344) while in subpopulation AMR AF= 0.0155 (237/15312). AF 95% confidence interval is 0.0147. There are 14 homozygotes in gnomad4. There are 803 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRB	NM_001379180.1 linkuse as main transcript	c.1300G>A	p.Val434Ile	missense_variant	7/7	ENST00000644823.1	NP_001366109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000644823.1 linkuse as main transcript	c.1300G>A	p.Val434Ile	missense_variant	7/7		NM_001379180.1	ENSP00000493776	P1
	ENST00000554926.1 linkuse as main transcript	n.415-2813C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1637

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0115

AC:

2872

AN:

249282

Hom.:

AF XY:

0.0116

AC XY:

1569

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.00231

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00718

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000981

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.0162

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0130

AC:

19017

AN:

1461106

Hom.:

187

Cov.:

AF XY:

0.0128

AC XY:

9328

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.0115

Gnomad4 ASJ exome

AF:

0.00670

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.0163

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.0107

AC:

1637

AN:

152344

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

803

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0102

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0127

AC:

109

ExAC

AF:

0.0110

AC:

1336

EpiCase

AF:

0.0216

EpiControl

AF:

0.0200

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 26, 2019	This variant is associated with the following publications: (PMID: 22951369, 29636544) -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 23, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	ESRRB: BP4, BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 30, 2012

Val413Ile in Exon 09 of ESRRB: This variant is not expected to have clinical sig nificance because it has been identified in 1.3% (91/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs146351534). -

Autosomal recessive nonsyndromic hearing loss 35

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.28

T;.;.;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.84

T;.;T;T

MetaRNN

Benign

0.0072

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.54

.;N;.;N

MutationTaster

Benign

0.73

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.11

N;N;.;N

REVEL

Benign

0.071

Sift

Benign

0.92

T;T;.;T

Sift4G

Benign

0.93

.;T;.;T

Polyphen

0.016

B;.;.;.

Vest4

0.061, 0.060

MPC

0.32

ClinPred

0.0072

GERP RS

-5.7

gMVP

0.054

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