Variant 14-76439434-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001379180.1(ESRRB):c.144C>A(p.Ile48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,613,444 control chromosomes in the GnomAD database, including 4,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 605 hom., cov: 33)

Exomes 𝑓: 0.063 ( 4309 hom. )

Consequence

ESRRB
NM_001379180.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.310

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 14-76439434-C-A is Benign according to our data. Variant chr14-76439434-C-A is described in ClinVar as [Benign]. Clinvar id is 45001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 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.144C>A	p.Ile48=	synonymous_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.144C>A	p.Ile48=	synonymous_variant	2/7		NM_001379180.1	ENSP00000493776	P1

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11603

AN:

152184

Hom.:

601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0918

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0855

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0526

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.0626

GnomAD3 exomes

AF:

0.0869

AC:

21504

AN:

247442

Hom.:

1338

AF XY:

0.0861

AC XY:

11597

AN XY:

134658

show subpopulations

Gnomad AFR exome

AF:

0.0902

Gnomad AMR exome

AF:

0.0905

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0570

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0681

GnomAD4 exome

AF:

0.0635

AC:

92781

AN:

1461142

Hom.:

4309

Cov.:

AF XY:

0.0652

AC XY:

47392

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.0905

Gnomad4 AMR exome

AF:

0.0885

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.134

Gnomad4 FIN exome

AF:

0.0590

Gnomad4 NFE exome

AF:

0.0505

Gnomad4 OTH exome

AF:

0.0721

GnomAD4 genome

AF:

0.0764

AC:

11633

AN:

152302

Hom.:

605

Cov.:

AF XY:

0.0799

AC XY:

5950

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0921

Gnomad4 AMR

AF:

0.0856

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.256

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.0526

Gnomad4 NFE

AF:

0.0537

Gnomad4 OTH

AF:

0.0619

Alfa

AF:

0.0546

Hom.:

105

Bravo

AF:

0.0757

Asia WGS

AF:

0.195

AC:

676

AN:

3478

EpiCase

AF:

0.0455

EpiControl

AF:

0.0439

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	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	Ile27Ile in Exon 04 of ESRRB: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 8.1% (301/3718) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs35544003). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

4.4

DANN

Benign

0.91

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