rs34497267

Variant names:

• chr7-1091758-G-A
• rs34497267
• NM_001098201.3:c.30G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001098201.3(GPER1):​c.30G>A​(p.Val10Val) 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
• Publications: 10 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.30G>A	p.Val10Val	synonymous_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+35499C>T		intron_variant	Intron 2 of 4	ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.30G>A	p.Val10Val	synonymous_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+35499C>T		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

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

GnomAD2 exomes AF: 0.0955 AC: 19222 AN: 201364 AF XY: 0.0982

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 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

African (AFR) AF: 0.0292 AC: 913 AN: 31294

American (AMR) AF: 0.0856 AC: 3008 AN: 35152

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3110 AN: 21642

East Asian (EAS) AF: 0.0393 AC: 1531 AN: 38950

South Asian (SAS) AF: 0.121 AC: 9090 AN: 74912

European-Finnish (FIN) AF: 0.0848 AC: 4275 AN: 50414

Middle Eastern (MID) AF: 0.0668 AC: 362 AN: 5420

European-Non Finnish (NFE) AF: 0.119 AC: 127733 AN: 1075288

Other (OTH) AF: 0.109 AC: 6230 AN: 57244

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

African (AFR) AF: 0.0346 AC: 1437 AN: 41582

American (AMR) AF: 0.0934 AC: 1430 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3472

East Asian (EAS) AF: 0.0534 AC: 276 AN: 5166

South Asian (SAS) AF: 0.114 AC: 549 AN: 4832

European-Finnish (FIN) AF: 0.0808 AC: 857 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7793 AN: 68014

Other (OTH) AF: 0.0945 AC: 200 AN: 2116

Alfa AF: 0.0982 Hom.: 469

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
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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