chr14-64234324-G-A

Position:

• chr14-64234324-G-A

Variant summary

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

The ENST00000341099.6(ESR2):​c.1406+646C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,464 control chromosomes in the GnomAD database, including 3,920 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 0.21 (3904 hom., cov: 31)
  • Exomes 𝑓: 0.20 (16 hom.)
• Consequence: ESR2 ENST00000341099.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.1406+646C>T		intron_variant		ENST00000341099.6	NP_001428.1
LOC124903328	XR_007064205.1	n.90-538G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.1406+646C>T		intron_variant		1	NM_001437.3	ENSP00000343925	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31741 AN: 151750 Hom.: 3911 Cov.: 31

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.205 AC: 122 AN: 596 Hom.: 16 Cov.: 0 AF XY: 0.201 AC XY: 73 AN XY: 364

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.209 AC: 31722 AN: 151868 Hom.: 3904 Cov.: 31 AF XY: 0.205 AC XY: 15251 AN XY: 74228

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.216

Alfa AF: 0.241 Hom.: 997

Bravo AF: 0.198

Asia WGS AF: 0.192 AC: 668 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	8.1
DANN	Benign	0.79

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: rs867443; hg19: chr14-64701042;