chr14-76439369-A-G

Position:

chr14-76439369-A-G

Variant summary

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

The NM_001379180.1(ESRRB):c.79A>G(p.Arg27Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00134 in 1,613,686 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 37 hom. )

Consequence

ESRRB
NM_001379180.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.05

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00788784).

BP6

Variant 14-76439369-A-G is Benign according to our data. Variant chr14-76439369-A-G is described in ClinVar as [Benign]. Clinvar id is 163416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-76439369-A-G is described in Lovd as [Likely_benign]. Variant chr14-76439369-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00162 (247/152334) while in subpopulation EAS AF= 0.0416 (215/5164). AF 95% confidence interval is 0.0371. There are 7 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRB	NM_001379180.1 linkuse as main transcript	c.79A>G	p.Arg27Gly	missense_variant	2/7	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.79A>G	p.Arg27Gly	missense_variant	2/7		NM_001379180.1	ENSP00000493776	P1

Frequencies

GnomAD3 genomes

AF:

0.00164

AC:

250

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0417

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00317

AC:

782

AN:

246644

Hom.:

AF XY:

0.00289

AC XY:

389

AN XY:

134448

show subpopulations

Gnomad AFR exome

AF:

0.000660

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0416

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000541

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00131

AC:

1909

AN:

1461352

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

928

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0420

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00296

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152334

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000288

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0416

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00190

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00319

AC:

387

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 04, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 16, 2013	Arg6Gly in exon 4 of ESRRB: This variant is not expected to have clinical signif icance because it has been identified in 1.7% (10/572) of Asian chromosomes by t he 1000 Genomes Project (dbSNP rs143477571) -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 03, 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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 12, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 35

Benign:1

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 rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Pathogenic

0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.;.;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

D;.;D;D

MetaRNN

Benign

0.0079

T;T;T;T

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.1

.;M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.2

N;N;.;N

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0020

D;D;.;D

Sift4G

Uncertain

0.025

.;D;.;D

Polyphen

0.97

D;.;.;.

Vest4

0.71

MVP

0.86

MPC

1.4

ClinPred

0.061

GERP RS

3.0

gMVP

0.63

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