rs944459

Positions:

• chr14-64232640-C-T

Variant summary

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

The NM_001437.3(ESR2):​c.*497G>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 0.0148 in 155,064 control chromosomes in the GnomAD database, including 315 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 0.015 (311 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (4 hom.)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.*497G>A		3_prime_UTR_variant	9/9	ENST00000341099.6	NP_001428.1
LOC124903328	XR_007064205.1	n.90-2222C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.*497G>A		3_prime_UTR_variant	9/9	1	NM_001437.3	ENSP00000343925	P1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2277 AN: 152110 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00616

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.0162

GnomAD4 exome AF: 0.00917 AC: 26 AN: 2836 Hom.: 4 Cov.: 0 AF XY: 0.00911 AC XY: 14 AN XY: 1536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00668

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000634

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0149 AC: 2273 AN: 152228 Hom.: 311 Cov.: 32 AF XY: 0.0174 AC XY: 1295 AN XY: 74446

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00615

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0191

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.00450 Hom.: 43

Bravo AF: 0.0155

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs944459; hg19: chr14-64699358;