rs4986938

chr14-64233098-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001437.3(ESR2):c.*39G>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 0.352 in 1,594,296 control chromosomes in the GnomAD database, including 102,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8374 hom., cov: 31)
  • Exomes 𝑓: 0.35 (93852 hom.)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-64233098-C-T is Benign according to our data. Variant chr14-64233098-C-T is described in ClinVar as [Benign]. Clinvar id is 1266011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001437.3	c.*39G>A		3_prime_UTR_variant	9/9	ENST00000341099.6
LOC124903328	XR_007064205.1	n.90-1764C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000341099.6	c.*39G>A		3_prime_UTR_variant	9/9	1	NM_001437.3	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49115 AN: 151878 Hom.: 8380 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.310 AC: 75935 AN: 244898 Hom.: 13063 AF XY: 0.318 AC XY: 41985 AN XY: 132172

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.109

Gnomad SAS exome AF: 0.289

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.355 AC: 511822 AN: 1442300 Hom.: 93852 Cov.: 34 AF XY: 0.354 AC XY: 252570 AN XY: 714176

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.323 AC: 49123 AN: 151996 Hom.: 8374 Cov.: 31 AF XY: 0.320 AC XY: 23803 AN XY: 74306

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.327

Alfa AF: 0.368 Hom.: 12393

Bravo AF: 0.312

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4986938; hg19: chr14-64699816; COSMIC: COSV50828487; COSMIC: COSV50828487;