rs8006145

Positions:

• chr14-64232732-C-A
• chr14-64232732-C-T

Variant summary

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

The ENST00000341099.6(ESR2):​c.*405G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 168,982 control chromosomes in the GnomAD database, including 5,412 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 (4908 hom., cov: 32)
  • Exomes 𝑓: 0.22 (504 hom.)
• Consequence: ESR2 ENST00000341099.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.*405G>T		3_prime_UTR_variant	9/9	ENST00000341099.6	NP_001428.1
LOC124903328	XR_007064205.1	n.90-2130C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.*405G>T		3_prime_UTR_variant	9/9	1	NM_001437.3	ENSP00000343925	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37769 AN: 152036 Hom.: 4913 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.220 AC: 3704 AN: 16828 Hom.: 504 Cov.: 2 AF XY: 0.221 AC XY: 1898 AN XY: 8590

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.0939

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.248 AC: 37778 AN: 152154 Hom.: 4908 Cov.: 32 AF XY: 0.244 AC XY: 18187 AN XY: 74412

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.256

Alfa AF: 0.280 Hom.: 11829

Bravo AF: 0.243

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.80
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8006145; hg19: chr14-64699450;