Variant rs1256049 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_001437.3(ESR2):c.984G>A(p.Val328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 1,613,366 control chromosomes in the GnomAD database, including 4,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 675 hom., cov: 31)

Exomes 𝑓: 0.044 ( 3351 hom. )

Consequence

ESR2
NM_001437.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0340

Variant links:

Genes affected

ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]

ESR2 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=-0.38).

BP6

Variant 14-64257333-C-T is Benign according to our data. Variant chr14-64257333-C-T is described in ClinVar as [Benign]. Clinvar id is 1228925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.034 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3 linkuse as main transcript	c.984G>A	p.Val328=	synonymous_variant	6/9	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6 linkuse as main transcript	c.984G>A	p.Val328=	synonymous_variant	6/9	1	NM_001437.3	ENSP00000343925	P1	Q92731-1

Frequencies

GnomAD3 genomes

AF:

0.0661

AC:

10050

AN:

152108

Hom.:

674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0441

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.0435

Gnomad FIN

AF:

0.0880

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0517

GnomAD3 exomes

AF:

0.0667

AC:

16779

AN:

251436

Hom.:

1557

AF XY:

0.0624

AC XY:

8474

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0913

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.368

Gnomad SAS exome

AF:

0.0336

Gnomad FIN exome

AF:

0.0798

Gnomad NFE exome

AF:

0.0355

Gnomad OTH exome

AF:

0.0490

GnomAD4 exome

AF:

0.0445

AC:

64963

AN:

1461140

Hom.:

3351

Cov.:

AF XY:

0.0438

AC XY:

31842

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.0923

Gnomad4 AMR exome

AF:

0.0388

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.320

Gnomad4 SAS exome

AF:

0.0332

Gnomad4 FIN exome

AF:

0.0781

Gnomad4 NFE exome

AF:

0.0329

Gnomad4 OTH exome

AF:

0.0567

GnomAD4 genome

AF:

0.0662

AC:

10080

AN:

152226

Hom.:

675

Cov.:

AF XY:

0.0687

AC XY:

5112

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0898

Gnomad4 AMR

AF:

0.0440

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.0435

Gnomad4 FIN

AF:

0.0880

Gnomad4 NFE

AF:

0.0364

Gnomad4 OTH

AF:

0.0540

Alfa

AF:

0.0409

Hom.:

259

Bravo

AF:

0.0651

Asia WGS

AF:

0.180

AC:

623

AN:

3478

EpiCase

AF:

0.0281

EpiControl

AF:

0.0314

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 11231990) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

ESR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.7

DANN

Benign

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