14-64269942-G-C

Variant names:

• chr14-64269942-G-C
• rs7154455
• NM_001437.3:c.536-1031C>G

Variant summary

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

The NM_001437.3(ESR2):​c.536-1031C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,966 control chromosomes in the GnomAD database, including 9,318 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 0.34 (9318 hom., cov: 32)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.536-1031C>G		intron_variant	Intron 3 of 8	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.536-1031C>G		intron_variant	Intron 3 of 8	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52001 AN: 151848 Hom.: 9320 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.342 AC: 52018 AN: 151966 Hom.: 9318 Cov.: 32 AF XY: 0.338 AC XY: 25113 AN XY: 74270

African (AFR) AF: 0.423 AC: 17505 AN: 41430

American (AMR) AF: 0.286 AC: 4370 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1480 AN: 3464

East Asian (EAS) AF: 0.219 AC: 1128 AN: 5162

South Asian (SAS) AF: 0.363 AC: 1745 AN: 4812

European-Finnish (FIN) AF: 0.250 AC: 2646 AN: 10570

Middle Eastern (MID) AF: 0.441 AC: 128 AN: 290

European-Non Finnish (NFE) AF: 0.322 AC: 21886 AN: 67968

Other (OTH) AF: 0.347 AC: 731 AN: 2106

Alfa AF: 0.196 Hom.: 431

Bravo AF: 0.343

Asia WGS AF: 0.299 AC: 1039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.57
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: rs7154455; hg19: chr14-64736660; COSMIC: COSV50838777;