14-64232214-G-T

Position:

• chr14-64232214-G-T

Variant summary

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

The NM_001437.3(ESR2):​c.*923C>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 0.651 in 152,016 control chromosomes in the GnomAD database, including 33,860 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 0.65 (33857 hom., cov: 30)
  • Exomes 𝑓: 0.45 (3 hom.)
• Consequence: ESR2 NM_001437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.*923C>A		3_prime_UTR_variant	9/9	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099	c.*923C>A		3_prime_UTR_variant	9/9	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98894 AN: 151856 Hom.: 33807 Cov.: 30

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.452 AC: 19 AN: 42 Hom.: 3 Cov.: 0 AF XY: 0.417 AC XY: 10 AN XY: 24

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.651 AC: 98998 AN: 151974 Hom.: 33857 Cov.: 30 AF XY: 0.647 AC XY: 48067 AN XY: 74276

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.628

Alfa AF: 0.600 Hom.: 3478

Bravo AF: 0.664

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1256065; hg19: chr14-64698932;