rs1256064

Positions:

• chr14-64234021-A-G

Variant summary

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

The ENST00000557772.5(ESR2):​c.*936T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,074 control chromosomes in the GnomAD database, including 7,348 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 (7347 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1 hom.)
• Consequence: ESR2 ENST00000557772.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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]

LOC124903328 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001437.3	c.1407-698T>C		intron_variant		ENST00000341099.6
LOC124903328	XR_007064205.1	n.90-841A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000341099.6	c.1407-698T>C		intron_variant		1	NM_001437.3	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37702 AN: 151926 Hom.: 7337 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.100 AC: 3 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.150 AC XY: 3 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.248 AC: 37753 AN: 152044 Hom.: 7347 Cov.: 32 AF XY: 0.249 AC XY: 18513 AN XY: 74334

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.231

Alfa AF: 0.124 Hom.: 2845

Bravo AF: 0.271

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1256064; hg19: chr14-64700739;