NM_001098201.3:c.789G>A

Variant names:

• chr7-1092517-G-A
• rs3808352
• NM_001098201.3:c.789G>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.789G>A​(p.Ala263Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,607,768 control chromosomes in the GnomAD database, including 25,073 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 0.14 (1777 hom., cov: 33)
  • Exomes 𝑓: 0.18 (23296 hom.)
• Consequence: GPER1 NM_001098201.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.47
• Publications: 18 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=-0.9).
• BP7: Synonymous conserved (PhyloP=-4.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPER1	NM_001098201.3	MANE Select	c.789G>A	p.Ala263Ala	synonymous	Exon 2 of 2	NP_001091671.1	Q99527
	CHLSN	NM_001318252.2	MANE Select	c.129+34740C>T		intron	N/A	NP_001305181.1	Q9BRJ6
	GPER1	NM_001039966.2		c.789G>A	p.Ala263Ala	synonymous	Exon 3 of 3	NP_001035055.1	Q99527

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPER1	ENST00000397088.4	TSL:1 MANE Select	c.789G>A	p.Ala263Ala	synonymous	Exon 2 of 2	ENSP00000380277.3	Q99527
	GPER1	ENST00000297469.3	TSL:1	c.789G>A	p.Ala263Ala	synonymous	Exon 2 of 2	ENSP00000297469.3	Q99527
	CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.129+34740C>T		intron	N/A	ENSP00000380286.3	Q9BRJ6

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21045 AN: 152128 Hom.: 1776 Cov.: 33

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.148

GnomAD2 exomes AF: 0.155 AC: 38019 AN: 245648 AF XY: 0.159

Gnomad AFR exome AF: 0.0475

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.0720

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.175 AC: 254802 AN: 1455522 Hom.: 23296 Cov.: 37 AF XY: 0.175 AC XY: 126526 AN XY: 724362

African (AFR) AF: 0.0435 AC: 1456 AN: 33476

American (AMR) AF: 0.123 AC: 5478 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6247 AN: 26122

East Asian (EAS) AF: 0.0840 AC: 3335 AN: 39698

South Asian (SAS) AF: 0.156 AC: 13493 AN: 86254

European-Finnish (FIN) AF: 0.146 AC: 6895 AN: 47288

Middle Eastern (MID) AF: 0.158 AC: 912 AN: 5766

European-Non Finnish (NFE) AF: 0.186 AC: 206605 AN: 1111858

Other (OTH) AF: 0.172 AC: 10381 AN: 60348

GnomAD4 genome AF: 0.138 AC: 21043 AN: 152246 Hom.: 1777 Cov.: 33 AF XY: 0.137 AC XY: 10184 AN XY: 74438

African (AFR) AF: 0.0487 AC: 2026 AN: 41560

American (AMR) AF: 0.142 AC: 2176 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3472

East Asian (EAS) AF: 0.0888 AC: 460 AN: 5178

South Asian (SAS) AF: 0.146 AC: 707 AN: 4828

European-Finnish (FIN) AF: 0.140 AC: 1488 AN: 10592

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12803 AN: 68000

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.157 Hom.: 1321

Bravo AF: 0.133

Asia WGS AF: 0.126 AC: 439 AN: 3478

EpiCase AF: 0.189

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.93
PhyloP100		-4.5
Mutation Taster		=97/3	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: rs3808352; hg19: chr7-1132153; COSMIC: COSV52468257; COSMIC: COSV52468257;