dbSNP rs8018687: ESR2:c.*169A>G (chr14-64227364-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001040275.1(ESR2):c.*169A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 697,990 control chromosomes in the GnomAD database, including 6,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3746 hom., cov: 32)

Exomes 𝑓: 0.082 ( 2981 hom. )

Consequence

ESR2
NM_001040275.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0130

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-64227364-T-C is Benign according to our data. Variant chr14-64227364-T-C is described in ClinVar as [Benign]. Clinvar id is 1237589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
ESR2	NM_001040275.1 link	c.*169A>G	3_prime_UTR_variant	Exon 9 of 9	NP_001035365.1	Q92731-2F1D8N3
ESR2	NM_001291712.2 link	c.*169A>G	3_prime_UTR_variant	Exon 14 of 14	NP_001278641.1	Q92731-2F1D8N3
ESR2	NM_001291723.1 link	c.*169A>G	3_prime_UTR_variant	Exon 9 of 9	NP_001278652.1	Q92731-2F1D8N3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ESR2	ENST00000353772 link	c.*169A>G	3_prime_UTR_variant	Exon 9 of 9	1	ENSP00000335551.4	Q92731-2
ESR2	ENST00000554572 link	c.*169A>G	3_prime_UTR_variant	Exon 14 of 14	1	ENSP00000450699.1	Q92731-2
ESR2	ENST00000556275.5 link	c.1406+7606A>G	intron_variant	Intron 8 of 8	2	ENSP00000452485.2	G3V5S2

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25085

AN:

152104

Hom.:

3739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.0980

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0285

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0629

Gnomad OTH

AF:

0.154

GnomAD4 exome

AF:

0.0817

AC:

44581

AN:

545768

Hom.:

2981

Cov.:

AF XY:

0.0835

AC XY:

23823

AN XY:

285240

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.0949

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.0764

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0320

Gnomad4 NFE exome

AF:

0.0619

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.165

AC:

25131

AN:

152222

Hom.:

3746

Cov.:

AF XY:

0.162

AC XY:

12064

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.0985

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.0285

Gnomad4 NFE

AF:

0.0629

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.0954

Hom.:

1208

Bravo

AF:

0.181

Asia WGS

AF:

0.125

AC:

435

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.8

DANN

Benign

0.41

Splicing

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