rs12435857

chr14-64256807-G-A

Variant summary

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

The NM_001437.3(ESR2):c.1091+419C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,952 control chromosomes in the GnomAD database, including 12,618 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 0.40 (12618 hom., cov: 32)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001437.3	c.1091+419C>T		intron_variant		ENST00000341099.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000341099.6	c.1091+419C>T		intron_variant		1	NM_001437.3	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61335 AN: 151832 Hom.: 12619 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.404 AC: 61362 AN: 151952 Hom.: 12618 Cov.: 32 AF XY: 0.399 AC XY: 29667 AN XY: 74296

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.402

Alfa AF: 0.424 Hom.: 6676

Bravo AF: 0.402

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.3
Dann	Benign	0.61

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: rs12435857; hg19: chr14-64723525;