rs34497267

chr7-1091758-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001098201.3(GPER1):c.30G>A(p.Val10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,542,620 control chromosomes in the GnomAD database, including 9,947 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 0.087 (717 hom., cov: 34)
  • Exomes 𝑓: 0.11 (9230 hom.)
• Consequence: GPER1 NM_001098201.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

Genes affected

GPER1 (HGNC:4485): (G protein-coupled estrogen receptor 1) This gene encodes a multi-pass membrane protein that localizes to the endoplasmic reticulum and a member of the G-protein coupled receptor 1 family. This receptor binds estrogen and activates multiple downstream signaling pathways, leading to stimulation of adenylate cyclase and an increase in cyclic AMP levels, while also promoting intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. This receptor has been shown to play a role in diverse biological processes, including bone and nervous system development, metabolism, cognition, male fertility and uterine function. [provided by RefSeq, Aug 2017]

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPER1	NM_001098201.3	c.30G>A	p.Val10=	synonymous_variant	2/2	ENST00000397088.4
C7orf50	NM_001318252.2	c.129+35499C>T		intron_variant		ENST00000397098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPER1	ENST00000397088.4	c.30G>A	p.Val10=	synonymous_variant	2/2	1	NM_001098201.3	P1
C7orf50	ENST00000397098.8	c.129+35499C>T		intron_variant		1	NM_001318252.2	P1

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13191 AN: 152186 Hom.: 716 Cov.: 34

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0931

GnomAD3 exomes AF: 0.0955 AC: 19222 AN: 201364 Hom.: 1063 AF XY: 0.0982 AC XY: 10507 AN XY: 106984

Gnomad AFR exome AF: 0.0331

Gnomad AMR exome AF: 0.0847

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.0419

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.0844

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.112 AC: 156252 AN: 1390316 Hom.: 9230 Cov.: 34 AF XY: 0.112 AC XY: 76581 AN XY: 683034

Gnomad4 AFR exome AF: 0.0292

Gnomad4 AMR exome AF: 0.0856

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.0393

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0848

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.0866 AC: 13196 AN: 152304 Hom.: 717 Cov.: 34 AF XY: 0.0854 AC XY: 6359 AN XY: 74464

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.0934

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0534

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0808

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0945

Alfa AF: 0.0998 Hom.: 334

Bravo AF: 0.0830

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.039
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs34497267; hg19: chr7-1131394; COSMIC: COSV52468980; COSMIC: COSV52468980;