rs3020443

Variant names:

• chr14-64325622-T-G
• rs3020443
• ENST00000554572.5:c.-768+10791A>C

Variant summary

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

The NM_001291712.2(ESR2):​c.-768+10791A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,974 control chromosomes in the GnomAD database, including 4,232 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 0.23 (4232 hom., cov: 31)
• Consequence: ESR2 NM_001291712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291712.2. 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_001291712.2		c.-768+10791A>C		intron	N/A	NP_001278641.1	Q92731-2
	ESR2	NM_001291723.1		c.-91+12276A>C		intron	N/A	NP_001278652.1	Q92731-2
	ESR2	NR_073496.2		n.716+12276A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000554572.5	TSL:1	c.-768+10791A>C		intron	N/A	ENSP00000450699.1	Q92731-2
	ESR2	ENST00000358599.9	TSL:2	c.-91+12276A>C		intron	N/A	ENSP00000351412.5	Q92731-2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35216 AN: 151856 Hom.: 4237 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.232 AC: 35203 AN: 151974 Hom.: 4232 Cov.: 31 AF XY: 0.226 AC XY: 16812 AN XY: 74284

African (AFR) AF: 0.218 AC: 9044 AN: 41444

American (AMR) AF: 0.191 AC: 2916 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3468

East Asian (EAS) AF: 0.119 AC: 617 AN: 5172

South Asian (SAS) AF: 0.234 AC: 1125 AN: 4798

European-Finnish (FIN) AF: 0.198 AC: 2089 AN: 10564

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17460 AN: 67950

Other (OTH) AF: 0.237 AC: 500 AN: 2114

Alfa AF: 0.247 Hom.: 8990

Bravo AF: 0.228

Asia WGS AF: 0.189 AC: 658 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.47
PhyloP100		-0.61
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: rs3020443; hg19: chr14-64792340;