rs1256059

Variant names:

• chr14-64243699-A-G
• rs1256059
• NM_001437.3:c.1225+5847T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-64243699-A-G
• chr14-64243699-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001437.3(ESR2):​c.1225+5847T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,058 control chromosomes in the GnomAD database, including 34,130 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 0.65 (34130 hom., cov: 31)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 23 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.1225+5847T>C		intron_variant	Intron 7 of 8	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.1225+5847T>C		intron_variant	Intron 7 of 8	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99382 AN: 151940 Hom.: 34079 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.654 AC: 99487 AN: 152058 Hom.: 34130 Cov.: 31 AF XY: 0.650 AC XY: 48284 AN XY: 74332

African (AFR) AF: 0.879 AC: 36450 AN: 41484

American (AMR) AF: 0.558 AC: 8531 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2179 AN: 3470

East Asian (EAS) AF: 0.691 AC: 3577 AN: 5174

South Asian (SAS) AF: 0.500 AC: 2411 AN: 4822

European-Finnish (FIN) AF: 0.572 AC: 6047 AN: 10570

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.561 AC: 38095 AN: 67948

Other (OTH) AF: 0.631 AC: 1330 AN: 2108

Alfa AF: 0.607 Hom.: 38793

Bravo AF: 0.667

Asia WGS AF: 0.607 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1256059; hg19: chr14-64710417;