chr14-64232173-C-T

Variant names:

• chr14-64232173-C-T
• rs1256066
• NM_001437.3:c.*964G>A

Variant summary

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

The NM_001437.3(ESR2):​c.*964G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 152,232 control chromosomes in the GnomAD database, including 995 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 0.082 (995 hom., cov: 31)
  • Exomes 𝑓: 0.038 (0 hom.)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	NM_001437.3	MANE Select	c.*964G>A		3_prime_UTR	Exon 9 of 9	NP_001428.1	Q92731-1
	ESR2	NM_001040275.1		c.1406+2797G>A		intron	N/A	NP_001035365.1	Q92731-2
	ESR2	NM_001291712.2		c.1406+2797G>A		intron	N/A	NP_001278641.1	Q92731-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000341099.6	TSL:1 MANE Select	c.*964G>A		3_prime_UTR	Exon 9 of 9	ENSP00000343925.4	Q92731-1
	ESR2	ENST00000557772.5	TSL:1	c.*2784G>A		3_prime_UTR	Exon 7 of 7	ENSP00000451582.1	Q92731-6
	ESR2	ENST00000353772.7	TSL:1	c.1406+2797G>A		intron	N/A	ENSP00000335551.4	Q92731-2

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 12423 AN: 152062 Hom.: 996 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0775

GnomAD4 exome AF: 0.0385 AC: 2 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.0357 AC XY: 1 AN XY: 28

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 20

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0817 AC: 12440 AN: 152180 Hom.: 995 Cov.: 31 AF XY: 0.0849 AC XY: 6315 AN XY: 74376

African (AFR) AF: 0.109 AC: 4536 AN: 41518

American (AMR) AF: 0.105 AC: 1604 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2361 AN: 5176

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4826

European-Finnish (FIN) AF: 0.0935 AC: 988 AN: 10568

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0373 AC: 2535 AN: 68010

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.0557 Hom.: 176

Bravo AF: 0.0883

Asia WGS AF: 0.208 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		0.070
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: rs1256066; hg19: chr14-64698891;