rs1256030

Positions:

• chr14-64280452-A-G
• chr14-64280452-A-T

Variant summary

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

The NM_001437.3(ESR2):​c.363-299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,972 control chromosomes in the GnomAD database, including 27,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (27735 hom., cov: 31)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-64280452-A-G is Benign according to our data. Variant chr14-64280452-A-G is described in ClinVar as [Benign]. Clinvar id is 1268833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.363-299T>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.363-299T>C		intron_variant		1	NM_001437.3	ENSP00000343925	P1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90524 AN: 151854 Hom.: 27706 Cov.: 31

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.596 AC: 90606 AN: 151972 Hom.: 27735 Cov.: 31 AF XY: 0.593 AC XY: 44024 AN XY: 74278

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.586

Alfa AF: 0.559 Hom.: 9653

Bravo AF: 0.604

Asia WGS AF: 0.585 AC: 2032 AN: 3478

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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1256030; hg19: chr14-64747170;