14-64230099-T-C

Variant names:

• chr14-64230099-T-C
• rs944458
• NM_001437.3:c.*3038A>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.*3038A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 150,302 control chromosomes in the GnomAD database, including 7,766 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 0.26 (7766 hom., cov: 28)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.*3038A>G		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.*3038A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38459 AN: 150192 Hom.: 7752 Cov.: 28

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.0664

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.256 AC: 38521 AN: 150302 Hom.: 7766 Cov.: 28 AF XY: 0.258 AC XY: 18874 AN XY: 73286

African (AFR) AF: 0.538 AC: 22075 AN: 41018

American (AMR) AF: 0.227 AC: 3406 AN: 14982

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 504 AN: 3456

East Asian (EAS) AF: 0.557 AC: 2818 AN: 5060

South Asian (SAS) AF: 0.172 AC: 816 AN: 4734

European-Finnish (FIN) AF: 0.128 AC: 1305 AN: 10172

Middle Eastern (MID) AF: 0.149 AC: 43 AN: 288

European-Non Finnish (NFE) AF: 0.104 AC: 7002 AN: 67606

Other (OTH) AF: 0.236 AC: 492 AN: 2082

Alfa AF: 0.198 Hom.: 631

Bravo AF: 0.278

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.86
PhyloP100		-0.90
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: rs944458; hg19: chr14-64696817;