14-76498312-C-T

Position:

chr14-76498312-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379180.1(ESRRB):c.1219C>T(p.Pro407Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,613,184 control chromosomes in the GnomAD database, including 4,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 357 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4033 hom. )

Consequence

ESRRB
NM_001379180.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 7.91

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:

ESRRB (HGNC:):

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=0.005125433).

BP6

Variant 14-76498312-C-T is Benign according to our data. Variant chr14-76498312-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 44995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRB	NM_001379180.1 linkuse as main transcript	c.1219C>T	p.Pro407Ser	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.1219C>T	p.Pro407Ser	missense_variant	7/7		NM_001379180.1	ENSP00000493776.1		A0A2R8Y491

Frequencies

GnomAD3 genomes

AF:

0.0616

AC:

9371

AN:

152182

Hom.:

357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0704

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0680

Gnomad OTH

AF:

0.0659

GnomAD3 exomes

AF:

0.0766

AC:

18998

AN:

248148

Hom.:

890

AF XY:

0.0742

AC XY:

9989

AN XY:

134702

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.0532

Gnomad EAS exome

AF:

0.110

Gnomad SAS exome

AF:

0.0706

Gnomad FIN exome

AF:

0.0507

Gnomad NFE exome

AF:

0.0692

Gnomad OTH exome

AF:

0.0753

GnomAD4 exome

AF:

0.0712

AC:

104043

AN:

1460884

Hom.:

4033

Cov.:

AF XY:

0.0709

AC XY:

51493

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.0215

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.0565

Gnomad4 EAS exome

AF:

0.0961

Gnomad4 SAS exome

AF:

0.0679

Gnomad4 FIN exome

AF:

0.0527

Gnomad4 NFE exome

AF:

0.0708

Gnomad4 OTH exome

AF:

0.0706

GnomAD4 genome

AF:

0.0615

AC:

9372

AN:

152300

Hom.:

357

Cov.:

AF XY:

0.0645

AC XY:

4806

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0705

Gnomad4 FIN

AF:

0.0488

Gnomad4 NFE

AF:

0.0680

Gnomad4 OTH

AF:

0.0652

Alfa

AF:

0.0648

Hom.:

565

Bravo

AF:

0.0637

TwinsUK

AF:

0.0763

AC:

283

ALSPAC

AF:

0.0747

AC:

288

ESP6500AA

AF:

0.0252

AC:

111

ESP6500EA

AF:

0.0680

AC:

585

ExAC

AF:

0.0712

AC:

8643

Asia WGS

AF:

0.108

AC:

375

AN:

3478

EpiCase

AF:

0.0677

EpiControl

AF:

0.0715

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Pro386Ser in Exon 09 of ESRRB: This variant is not expected to have clinical sig nificance because it has been identified in 6.9% (481/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs35774316). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 12, 2018	- -

Autosomal recessive nonsyndromic hearing loss 35

Benign:2

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

D;.;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

T;.;T;T

MetaRNN

Benign

0.0051

T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

.;L;.;L

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.4

N;N;.;N

REVEL

Pathogenic

0.68

Sift

Benign

0.45

T;T;.;T

Sift4G

Benign

0.72

.;T;.;T

Polyphen

0.60

P;.;.;.

Vest4

0.34, 0.32

MPC

0.60

ClinPred

0.026

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.55

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