rs1887994

chr14-64293893-C-A

Variant summary

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

The NM_001437.3(ESR2):c.-91+140G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,326 control chromosomes in the GnomAD database, including 523 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 0.075 (522 hom., cov: 33)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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 = 0.0939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001437.3	c.-91+140G>T		intron_variant		ENST00000341099.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000341099.6	c.-91+140G>T		intron_variant		1	NM_001437.3	P1

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11401 AN: 152202 Hom.: 524 Cov.: 33

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.0716

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 1 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.0748 AC: 11398 AN: 152320 Hom.: 522 Cov.: 33 AF XY: 0.0749 AC XY: 5579 AN XY: 74480

Gnomad4 AFR AF: 0.0474

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.00327

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0959

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0905 Hom.: 916

Bravo AF: 0.0708

Asia WGS AF: 0.0250 AC: 85 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	5.9
Dann	Benign	0.65

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: rs1887994; hg19: chr14-64760611;