rs1255998

chr14-64227153-G-Cchr14-64227153-G-T

Variant summary

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

The ENST00000353772.7(ESR2):c.*380C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 233,964 control chromosomes in the GnomAD database, including 9,064 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 0.25 (7833 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1231 hom.)
• Consequence: ESR2 ENST00000353772.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001040275.1	c.*380C>G		3_prime_UTR_variant	9/9
ESR2	NM_001214902.1	c.*737C>G		3_prime_UTR_variant	8/8
ESR2	NM_001291712.2	c.*380C>G		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000353772.7	c.*380C>G		3_prime_UTR_variant	9/9	1
ESR2	ENST00000554572.5	c.*380C>G		3_prime_UTR_variant	14/14	1
ESR2	ENST00000556275.5	c.1406+7817C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38512 AN: 151976 Hom.: 7818 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.133 AC: 10860 AN: 81870 Hom.: 1231 Cov.: 0 AF XY: 0.133 AC XY: 5585 AN XY: 42130

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.254 AC: 38576 AN: 152094 Hom.: 7833 Cov.: 32 AF XY: 0.254 AC XY: 18867 AN XY: 74342

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.234

Alfa AF: 0.0547 Hom.: 71

Bravo AF: 0.277

Asia WGS AF: 0.332 AC: 1151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.66
Dann	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1255998; hg19: chr14-64693871;