rs3020444

Variant names:

• chr14-64324295-A-G
• rs3020444
• ENST00000554572.5:c.-768+12118T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-64324295-A-G
• chr14-64324295-A-T

Variant summary

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

The ENST00000554572.5(ESR2):​c.-768+12118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,964 control chromosomes in the GnomAD database, including 10,519 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 0.36 (10519 hom., cov: 32)
• Consequence: ESR2 ENST00000554572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001291712.2	c.-768+12118T>C		intron_variant	Intron 2 of 13		NP_001278641.1
ESR2	NM_001291723.1	c.-91+13603T>C		intron_variant	Intron 1 of 8		NP_001278652.1
ESR2	NR_073496.2	n.716+13603T>C		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000554572.5	c.-768+12118T>C		intron_variant	Intron 2 of 13	1		ENSP00000450699.1
ESR2	ENST00000358599.9	c.-91+13603T>C		intron_variant	Intron 1 of 8	2		ENSP00000351412.5

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54592 AN: 151846 Hom.: 10517 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.359 AC: 54617 AN: 151964 Hom.: 10519 Cov.: 32 AF XY: 0.352 AC XY: 26157 AN XY: 74252

African (AFR) AF: 0.492 AC: 20360 AN: 41378

American (AMR) AF: 0.301 AC: 4594 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1432 AN: 3472

East Asian (EAS) AF: 0.209 AC: 1082 AN: 5170

South Asian (SAS) AF: 0.348 AC: 1676 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2380 AN: 10572

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21805 AN: 67978

Other (OTH) AF: 0.363 AC: 766 AN: 2112

Alfa AF: 0.271 Hom.: 1401

Bravo AF: 0.366

Asia WGS AF: 0.296 AC: 1030 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.61
PhyloP100		1.1
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: rs3020444; hg19: chr14-64791013;