chr14-64278407-C-T

Variant names:

• chr14-64278407-C-T
• rs1256034
• NM_001437.3:c.535+1574G>A

Variant summary

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

The NM_001437.3(ESR2):​c.535+1574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 152,216 control chromosomes in the GnomAD database, including 521 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 0.046 (521 hom., cov: 32)
• Consequence: ESR2 NM_001437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3	c.535+1574G>A		intron_variant	Intron 3 of 8	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.535+1574G>A		intron_variant	Intron 3 of 8	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6964 AN: 152098 Hom.: 522 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.0382

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0458 AC: 6975 AN: 152216 Hom.: 521 Cov.: 32 AF XY: 0.0497 AC XY: 3699 AN XY: 74424

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0387

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0407 Hom.: 37

Bravo AF: 0.0412

Asia WGS AF: 0.170 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.95
DANN	Benign	0.34

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: rs1256034; hg19: chr14-64745125;