rs1271572

Positions:

• chr14-64295199-A-C
• chr14-64295199-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000554572.5(ESR2):​c.-91+2334T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 146,246 control chromosomes in the GnomAD database, including 26,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (26179 hom., cov: 32)
• Consequence: ESR2 ENST00000554572.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.131

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 14-64295199-A-C is Benign according to our data. Variant chr14-64295199-A-C is described in ClinVar as [Benign]. Clinvar id is 1236069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001291712.2	c.-91+2334T>G		intron_variant			NP_001278641.1
ESR2	NM_001291723.1	c.-90-12124T>G		intron_variant			NP_001278652.1
ESR2	XM_047431076.1	c.-90-12124T>G		intron_variant			XP_047287032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000554572.5	c.-91+2334T>G		intron_variant		1		ENSP00000450699
ESR2	ENST00000358599.9	c.-90-12124T>G		intron_variant		2		ENSP00000351412

Frequencies

GnomAD3 genomes AF: 0.601 AC: 87852 AN: 146132 Hom.: 26152 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.507

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.601 AC: 87930 AN: 146246 Hom.: 26179 Cov.: 32 AF XY: 0.596 AC XY: 42657 AN XY: 71556

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.601

Alfa AF: 0.561 Hom.: 23887

Bravo AF: 0.590

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2019

This variant is associated with the following publications: (PMID: 30823486) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1271572; hg19: chr14-64761917;