chr14-64228369-A-G

Variant names:

• chr14-64228369-A-G
• rs1152579
• NM_001437.3:c.*4768T>C

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.*4768T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,104 control chromosomes in the GnomAD database, including 34,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (34711 hom., cov: 32)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610
• Publications: 16 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)

LOC124903328 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-64228369-A-G is Benign according to our data. Variant chr14-64228369-A-G is described in ClinVar as Benign. ClinVar VariationId is 1259718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.*4768T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.*4768T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100347 AN: 151986 Hom.: 34659 Cov.: 32

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.660 AC: 100454 AN: 152104 Hom.: 34711 Cov.: 32 AF XY: 0.656 AC XY: 48762 AN XY: 74344

African (AFR) AF: 0.880 AC: 36537 AN: 41518

American (AMR) AF: 0.563 AC: 8597 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2223 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3613 AN: 5178

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4822

European-Finnish (FIN) AF: 0.581 AC: 6128 AN: 10554

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38687 AN: 67982

Other (OTH) AF: 0.639 AC: 1347 AN: 2108

Alfa AF: 0.723 Hom.: 9344

Bravo AF: 0.673

Asia WGS AF: 0.617 AC: 2144 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	-0.87
CADD	Benign	4.9
DANN	Benign	0.65
PhyloP100		-0.061
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1152579; hg19: chr14-64695087;