rs1256062

Positions:

• chr14-64236600-T-C

Variant summary

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

The NM_001437.3(ESR2):​c.1226-1450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,982 control chromosomes in the GnomAD database, including 4,578 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 0.21 (4578 hom., cov: 31)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.1226-1450A>G		intron_variant		ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.1226-1450A>G		intron_variant		1	NM_001437.3	ENSP00000343925	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31848 AN: 151864 Hom.: 4574 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.210 AC: 31878 AN: 151982 Hom.: 4578 Cov.: 31 AF XY: 0.211 AC XY: 15693 AN XY: 74304

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.200

Alfa AF: 0.150 Hom.: 1239

Bravo AF: 0.219

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.42

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: rs1256062; hg19: chr14-64703318;