chr14-64234738-C-G

Position:

• chr14-64234738-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000557772.5(ESR2):​c.*219G>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 0.0486 in 928,502 control chromosomes in the GnomAD database, including 2,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (559 hom., cov: 32)
  • Exomes 𝑓: 0.047 (2228 hom.)
• Consequence: ESR2 ENST00000557772.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0160

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]

ESR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-64234738-C-G is Benign according to our data. Variant chr14-64234738-C-G is described in ClinVar as [Benign]. Clinvar id is 1282534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.1406+232G>C		intron_variant		ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.1406+232G>C		intron_variant		1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8477 AN: 152098 Hom.: 562 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0444

GnomAD4 exome AF: 0.0472 AC: 36641 AN: 776286 Hom.: 2228 Cov.: 10 AF XY: 0.0463 AC XY: 17926 AN XY: 387206

Gnomad4 AFR exome AF: 0.0519

Gnomad4 AMR exome AF: 0.0365

Gnomad4 ASJ exome AF: 0.0121

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.0267

Gnomad4 FIN exome AF: 0.0769

Gnomad4 NFE exome AF: 0.0335

Gnomad4 OTH exome AF: 0.0532

GnomAD4 genome AF: 0.0557 AC: 8479 AN: 152216 Hom.: 559 Cov.: 32 AF XY: 0.0587 AC XY: 4371 AN XY: 74420

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.0365

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0477 Hom.: 33

Bravo AF: 0.0528

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.92
CADD	Benign	4.0
DANN	Benign	0.38

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: rs944460; hg19: chr14-64701456;