rs8018687

chr14-64227364-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000353772.7(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 ENST00000353772.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001040275.1	c.*169A>G		3_prime_UTR_variant	9/9
ESR2	NM_001214902.1	c.*526A>G		3_prime_UTR_variant	8/8
ESR2	NM_001291712.2	c.*169A>G		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000353772.7	c.*169A>G		3_prime_UTR_variant	9/9	1
ESR2	ENST00000554572.5	c.*169A>G		3_prime_UTR_variant	14/14	1
ESR2	ENST00000556275.5	c.1406+7606A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25085 AN: 152104 Hom.: 3739 Cov.: 32

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.: 7 AF XY: 0.0835 AC XY: 23823 AN XY: 285240

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.: 32 AF XY: 0.162 AC XY: 12064 AN XY: 74424

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:1

Revision: criteria provided, single submitter

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	-0.82
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

Other links and lift over

dbSNP: rs8018687; hg19: chr14-64694082; COSMIC: COSV59939092; COSMIC: COSV59939092;