rs1256120

Positions:

• chr14-64338283-A-G
• chr14-64338283-A-T

Variant summary

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

The NM_001291712.2(ESR2):​c.-1461T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 155,434 control chromosomes in the GnomAD database, including 3,602 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 0.20 (3564 hom., cov: 32)
  • Exomes 𝑓: 0.13 (38 hom.)
• Consequence: ESR2 NM_001291712.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

ENSG00000214770 (HGNC:):

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001291712.2	c.-1461T>C		5_prime_UTR_variant	1/14		NP_001278641.1
ESR2	NM_001291723.1	c.-476T>C		5_prime_UTR_variant	1/9		NP_001278652.1
ESR2	XM_047431076.1	c.-784T>C		5_prime_UTR_variant	1/10		XP_047287032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000214770	ENST00000359491.1	n.317T>C		non_coding_transcript_exon_variant	1/3	1
ENSG00000214770	ENST00000648279.1	n.357T>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30089 AN: 151928 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.0970

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.132 AC: 447 AN: 3388 Hom.: 38 Cov.: 0 AF XY: 0.144 AC XY: 278 AN XY: 1924

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.198 AC: 30151 AN: 152046 Hom.: 3564 Cov.: 32 AF XY: 0.199 AC XY: 14782 AN XY: 74330

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.187

Alfa AF: 0.176 Hom.: 354

Bravo AF: 0.210

Asia WGS AF: 0.263 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1256120; hg19: chr14-64805001; COSMIC: COSV104421842;