rs12702047

Variant names:

• chr7-1093084-G-A
• rs12702047
• NM_001098201.3:c.*228G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098201.3(GPER1):​c.*228G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 684,992 control chromosomes in the GnomAD database, including 9,595 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 0.15 (1854 hom., cov: 32)
  • Exomes 𝑓: 0.17 (7741 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*228G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+34173C>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.*228G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+34173C>T		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22412 AN: 151950 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.167 AC: 24573 AN: 146768 AF XY: 0.167

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.0626

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.165 AC: 87938 AN: 532924 Hom.: 7741 Cov.: 3 AF XY: 0.165 AC XY: 47542 AN XY: 288400

African (AFR) AF: 0.104 AC: 1588 AN: 15296

American (AMR) AF: 0.216 AC: 7276 AN: 33740

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2131 AN: 19326

East Asian (EAS) AF: 0.0845 AC: 2509 AN: 29694

South Asian (SAS) AF: 0.179 AC: 11049 AN: 61706

European-Finnish (FIN) AF: 0.211 AC: 8326 AN: 39542

Middle Eastern (MID) AF: 0.122 AC: 485 AN: 3976

European-Non Finnish (NFE) AF: 0.167 AC: 50248 AN: 300536

Other (OTH) AF: 0.149 AC: 4326 AN: 29108

GnomAD4 genome AF: 0.147 AC: 22430 AN: 152068 Hom.: 1854 Cov.: 32 AF XY: 0.147 AC XY: 10930 AN XY: 74338

African (AFR) AF: 0.108 AC: 4460 AN: 41486

American (AMR) AF: 0.163 AC: 2484 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.0659 AC: 340 AN: 5156

South Asian (SAS) AF: 0.178 AC: 855 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10568

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11404 AN: 67972

Other (OTH) AF: 0.137 AC: 289 AN: 2114

Alfa AF: 0.154 Hom.: 458

Bravo AF: 0.144

Asia WGS AF: 0.124 AC: 429 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	1.1
DANN	Benign	0.58
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs12702047; hg19: chr7-1132720;