Variant rs4986938 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001437.3(ESR2):c.*39G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,594,296 control chromosomes in the GnomAD database, including 102,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8374 hom., cov: 31)

Exomes 𝑓: 0.35 ( 93852 hom. )

Consequence

ESR2
NM_001437.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.222

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 14-64233098-C-T is Benign according to our data. Variant chr14-64233098-C-T is described in ClinVar as [Benign]. Clinvar id is 1266011.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001437.3 linkuse as main transcript	c.*39G>A		3_prime_UTR_variant	9/9	ENST00000341099.6
LOC124903328	XR_007064205.1 linkuse as main transcript	n.90-1764C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000341099.6 linkuse as main transcript	c.*39G>A		3_prime_UTR_variant	9/9	1	NM_001437.3	P1	Q92731-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49115

AN:

151878

Hom.:

8380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.332

GnomAD3 exomes

AF:

0.310

AC:

75935

AN:

244898

Hom.:

13063

AF XY:

0.318

AC XY:

41985

AN XY:

132172

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.355

AC:

511822

AN:

1442300

Hom.:

93852

Cov.:

AF XY:

0.354

AC XY:

252570

AN XY:

714176

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.420

Gnomad4 EAS exome

AF:

0.134

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.356

Gnomad4 NFE exome

AF:

0.375

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.323

AC:

49123

AN:

151996

Hom.:

8374

Cov.:

AF XY:

0.320

AC XY:

23803

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.267

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.375

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.368

Hom.:

12393

Bravo

AF:

0.312

Asia WGS

AF:

0.232

AC:

809

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.2

DANN

Benign

0.73

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