rs1256031

chr14-64279461-G-Achr14-64279461-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001437.3(ESR2):c.535+520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,822 control chromosomes in the GnomAD database, including 24,697 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24697 hom., cov: 31)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001437.3	c.535+520C>T		intron_variant		ENST00000341099.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000341099.6	c.535+520C>T		intron_variant		1	NM_001437.3	P1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85639 AN: 151702 Hom.: 24681 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 85694 AN: 151822 Hom.: 24697 Cov.: 31 AF XY: 0.561 AC XY: 41604 AN XY: 74168

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.545

Alfa AF: 0.534 Hom.: 21808

Bravo AF: 0.561

Asia WGS AF: 0.522 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.99
Dann	Benign	0.57

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

Other links and lift over

dbSNP: rs1256031; hg19: chr14-64746179; COSMIC: COSV99963490;