ENST00000554572.5:c.-767-3015T>C

Variant names:

• chr14-64306674-A-G
• rs3020449
• ENST00000554572.5:c.-767-3015T>C

Variant summary

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

The ENST00000554572.5(ESR2):​c.-767-3015T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,078 control chromosomes in the GnomAD database, including 22,481 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 0.52 (22481 hom., cov: 33)
• Consequence: ESR2 ENST00000554572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 24 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000554572.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	NM_001291712.2		c.-767-3015T>C		intron	N/A	NP_001278641.1
	ESR2	NM_001291723.1		c.-90-23599T>C		intron	N/A	NP_001278652.1
	ESR2	NR_073496.2		n.717-23599T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000554572.5	TSL:1	c.-767-3015T>C		intron	N/A	ENSP00000450699.1
	ESR2	ENST00000358599.9	TSL:2	c.-90-23599T>C		intron	N/A	ENSP00000351412.5

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78504 AN: 151960 Hom.: 22449 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.517 AC: 78583 AN: 152078 Hom.: 22481 Cov.: 33 AF XY: 0.506 AC XY: 37652 AN XY: 74360

African (AFR) AF: 0.777 AC: 32249 AN: 41478

American (AMR) AF: 0.457 AC: 6986 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1617 AN: 5176

South Asian (SAS) AF: 0.406 AC: 1958 AN: 4828

European-Finnish (FIN) AF: 0.333 AC: 3523 AN: 10566

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28703 AN: 67964

Other (OTH) AF: 0.509 AC: 1077 AN: 2116

Alfa AF: 0.460 Hom.: 4059

Bravo AF: 0.539

Asia WGS AF: 0.390 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.88
PhyloP100		-2.9
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: rs3020449; hg19: chr14-64773392;