rs1952585

Positions:

• chr14-64245637-A-G

Variant summary

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

The NM_001437.3(ESR2):​c.1225+3909T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,856 control chromosomes in the GnomAD database, including 6,439 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 0.22 (6439 hom., cov: 31)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.1225+3909T>C		intron_variant		ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.1225+3909T>C		intron_variant		1	NM_001437.3	ENSP00000343925	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33412 AN: 151742 Hom.: 6421 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.0831

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.220 AC: 33473 AN: 151856 Hom.: 6439 Cov.: 31 AF XY: 0.217 AC XY: 16097 AN XY: 74204

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0831

Gnomad4 OTH AF: 0.213

Alfa AF: 0.153 Hom.: 761

Bravo AF: 0.249

Asia WGS AF: 0.169 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.20
DANN	Benign	0.31

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: rs1952585; hg19: chr14-64712355;