14-64296881-G-A

Position:

• chr14-64296881-G-A

Variant summary

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

The ENST00000554572.5(ESR2):​c.-91+652C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 152,304 control chromosomes in the GnomAD database, including 70 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 0.016 (70 hom., cov: 32)
• Consequence: ESR2 ENST00000554572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001291712.2	c.-91+652C>T		intron_variant			NP_001278641.1
ESR2	NM_001291723.1	c.-90-13806C>T		intron_variant			NP_001278652.1
ESR2	XM_047431076.1	c.-90-13806C>T		intron_variant			XP_047287032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000554572.5	c.-91+652C>T		intron_variant		1		ENSP00000450699
ESR2	ENST00000358599.9	c.-90-13806C>T		intron_variant		2		ENSP00000351412

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2485 AN: 152186 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0164 AC: 2495 AN: 152304 Hom.: 70 Cov.: 32 AF XY: 0.0172 AC XY: 1281 AN XY: 74476

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0864

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0119 Hom.: 32

Bravo AF: 0.0244

Asia WGS AF: 0.0360 AC: 123 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	9.3
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: rs10483774; hg19: chr14-64763599;