rs58262369

chr14-64227194-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000353772.7(ESR2):c.*339G>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 0.017 in 308,098 control chromosomes in the GnomAD database, including 180 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 0.024 (119 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (61 hom.)
• Consequence: ESR2 ENST00000353772.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001040275.1	c.*339G>A		3_prime_UTR_variant	9/9
ESR2	NM_001214902.1	c.*696G>A		3_prime_UTR_variant	8/8
ESR2	NM_001291712.2	c.*339G>A		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000353772.7	c.*339G>A		3_prime_UTR_variant	9/9	1
ESR2	ENST00000554572.5	c.*339G>A		3_prime_UTR_variant	14/14	1
ESR2	ENST00000556275.5	c.1406+7776G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3680 AN: 152226 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.00994 AC: 1548 AN: 155754 Hom.: 61 Cov.: 0 AF XY: 0.00945 AC XY: 762 AN XY: 80616

Gnomad4 AFR exome AF: 0.0443

Gnomad4 AMR exome AF: 0.0919

Gnomad4 ASJ exome AF: 0.000594

Gnomad4 EAS exome AF: 0.0725

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.00418

Gnomad4 NFE exome AF: 0.000795

Gnomad4 OTH exome AF: 0.0134

GnomAD4 genome AF: 0.0242 AC: 3692 AN: 152344 Hom.: 119 Cov.: 32 AF XY: 0.0244 AC XY: 1821 AN XY: 74492

Gnomad4 AFR AF: 0.0497

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0110 Hom.: 11

Bravo AF: 0.0335

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.8
Dann	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs58262369; hg19: chr14-64693912;