rs1256030

Variant names:

• chr14-64280452-A-G
• rs1256030
• NM_001437.3:c.363-299T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 publications found

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]

ESR2 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
• familial medullary thyroid carcinoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ovarian dysgenesis 8

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.363-299T>C		intron_variant	Intron 2 of 8	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.363-299T>C		intron_variant	Intron 2 of 8	1	NM_001437.3	ENSP00000343925.4

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

African (AFR) AF: 0.726 AC: 30094 AN: 41468

American (AMR) AF: 0.531 AC: 8095 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3550 AN: 5160

South Asian (SAS) AF: 0.454 AC: 2189 AN: 4822

European-Finnish (FIN) AF: 0.555 AC: 5866 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36750 AN: 67936

Other (OTH) AF: 0.586 AC: 1232 AN: 2104

Alfa AF: 0.562 Hom.: 11738

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

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.54
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1256030; hg19: chr14-64747170;