chr14-64232173-C-T

Position:

• chr14-64232173-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.*964G>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 0.0817 in 152,232 control chromosomes in the GnomAD database, including 995 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 0.082 (995 hom., cov: 31)
  • Exomes 𝑓: 0.038 (0 hom.)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR2	NM_001437.3	c.*964G>A		3_prime_UTR_variant	9/9	ENST00000341099.6
LOC124903328	XR_007064205.1	n.90-2689C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR2	ENST00000341099.6	c.*964G>A		3_prime_UTR_variant	9/9	1	NM_001437.3	P1

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 12423 AN: 152062 Hom.: 996 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0775

GnomAD4 exome AF: 0.0385 AC: 2 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.0357 AC XY: 1 AN XY: 28

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0817 AC: 12440 AN: 152180 Hom.: 995 Cov.: 31 AF XY: 0.0849 AC XY: 6315 AN XY: 74376

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.0408

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0545 Hom.: 143

Bravo AF: 0.0883

Asia WGS AF: 0.208 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.4
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1256066; hg19: chr14-64698891;