rs944050

Positions:

chr14-64233327-T-C

Variant summary

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

The NM_001437.3(ESR2):c.1407-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,606,512 control chromosomes in the GnomAD database, including 6,384 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 1003 hom., cov: 31)

Exomes 𝑓: 0.052 ( 5381 hom. )

Consequence

ESR2
NM_001437.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004588

Clinical Significance

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

Conservation

PhyloP100: -0.724

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:

LOC124903328 (HGNC:):

LOC124903328 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 (BayesDel_noAF=-0.65).

BP6

Variant 14-64233327-T-C is Benign according to our data. Variant chr14-64233327-T-C is described in ClinVar as [Benign]. Clinvar id is 1267790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 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.1407-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000341099.6	NP_001428.1
LOC124903328	XR_007064205.1 linkuse as main transcript	n.90-1535T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6 linkuse as main transcript	c.1407-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001437.3	ENSP00000343925	P1	Q92731-1

Frequencies

GnomAD3 genomes

AF:

0.0820

AC:

12468

AN:

152034

Hom.:

1003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00662

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.0411

Gnomad FIN

AF:

0.0936

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0374

Gnomad OTH

AF:

0.0774

GnomAD3 exomes

AF:

0.0949

AC:

23740

AN:

250152

Hom.:

2906

AF XY:

0.0847

AC XY:

11447

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.470

Gnomad SAS exome

AF:

0.0304

Gnomad FIN exome

AF:

0.0846

Gnomad NFE exome

AF:

0.0365

Gnomad OTH exome

AF:

0.0644

GnomAD4 exome

AF:

0.0519

AC:

75444

AN:

1454360

Hom.:

5381

Cov.:

AF XY:

0.0502

AC XY:

36241

AN XY:

721828

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.0128

Gnomad4 EAS exome

AF:

0.403

Gnomad4 SAS exome

AF:

0.0299

Gnomad4 FIN exome

AF:

0.0831

Gnomad4 NFE exome

AF:

0.0336

Gnomad4 OTH exome

AF:

0.0668

GnomAD4 genome

AF:

0.0821

AC:

12487

AN:

152152

Hom.:

1003

Cov.:

AF XY:

0.0853

AC XY:

6343

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.456

Gnomad4 SAS

AF:

0.0409

Gnomad4 FIN

AF:

0.0936

Gnomad4 NFE

AF:

0.0374

Gnomad4 OTH

AF:

0.0794

Alfa

AF:

0.0500

Hom.:

292

Bravo

AF:

0.0888

Asia WGS

AF:

0.208

AC:

721

AN:

3478

EpiCase

AF:

0.0287

EpiControl

AF:

0.0321

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	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 16553027) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.65

CADD

Benign

7.6

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000046

dbscSNV1_RF

Benign

0.030

SpliceAI score (max)

0.020

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