rs17101774

Positions:

• chr14-64326863-T-C

Variant summary

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

The ENST00000554572.5(ESR2):​c.-768+9550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,304 control chromosomes in the GnomAD database, including 319 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 0.045 (319 hom., cov: 32)
• Consequence: ESR2 ENST00000554572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001291712.2	c.-768+9550A>G		intron_variant			NP_001278641.1
ESR2	NM_001291723.1	c.-91+11035A>G		intron_variant			NP_001278652.1
ESR2	XM_047431076.1	c.-91+9550A>G		intron_variant			XP_047287032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000554572.5	c.-768+9550A>G		intron_variant		1		ENSP00000450699
ESR2	ENST00000358599.9	c.-91+11035A>G		intron_variant		2		ENSP00000351412

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6776 AN: 152186 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0377

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

GnomAD4 genome AF: 0.0446 AC: 6788 AN: 152304 Hom.: 319 Cov.: 32 AF XY: 0.0432 AC XY: 3216 AN XY: 74468

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.00593

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0248 Hom.: 85

Bravo AF: 0.0489

Asia WGS AF: 0.0160 AC: 56 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	0.13
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17101774; hg19: chr14-64793581;