rs8006145

Variant names:

• chr14-64232732-C-A
• rs8006145
• NM_001437.3:c.*405G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-64232732-C-A
• chr14-64232732-C-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.*405G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 168,982 control chromosomes in the GnomAD database, including 5,412 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 0.25 (4908 hom., cov: 32)
  • Exomes 𝑓: 0.22 (504 hom.)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 22 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.*405G>T		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.*405G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37769 AN: 152036 Hom.: 4913 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.220 AC: 3704 AN: 16828 Hom.: 504 Cov.: 2 AF XY: 0.221 AC XY: 1898 AN XY: 8590

African (AFR) AF: 0.152 AC: 115 AN: 758

American (AMR) AF: 0.151 AC: 346 AN: 2298

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 126 AN: 442

East Asian (EAS) AF: 0.0939 AC: 102 AN: 1086

South Asian (SAS) AF: 0.197 AC: 194 AN: 986

European-Finnish (FIN) AF: 0.228 AC: 103 AN: 452

Middle Eastern (MID) AF: 0.269 AC: 14 AN: 52

European-Non Finnish (NFE) AF: 0.251 AC: 2481 AN: 9874

Other (OTH) AF: 0.253 AC: 223 AN: 880

GnomAD4 genome AF: 0.248 AC: 37778 AN: 152154 Hom.: 4908 Cov.: 32 AF XY: 0.244 AC XY: 18187 AN XY: 74412

African (AFR) AF: 0.213 AC: 8857 AN: 41486

American (AMR) AF: 0.206 AC: 3157 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3472

East Asian (EAS) AF: 0.120 AC: 623 AN: 5178

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2488 AN: 10596

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19141 AN: 67988

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.273 Hom.: 22918

Bravo AF: 0.243

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.80
DANN	Benign	0.26
PhyloP100		-0.64
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: rs8006145; hg19: chr14-64699450;