rs3808353

chr7-1093336-G-Achr7-1093336-G-T

Variant summary

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

The NM_001098201.3(GPER1):c.*480G>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 0.176 in 421,264 control chromosomes in the GnomAD database, including 7,055 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 0.17 (2421 hom., cov: 33)
  • Exomes 𝑓: 0.18 (4634 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPER1	NM_001098201.3	c.*480G>A		3_prime_UTR_variant	2/2	ENST00000397088.4
C7orf50	NM_001318252.2	c.129+33921C>T		intron_variant		ENST00000397098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPER1	ENST00000397088.4	c.*480G>A		3_prime_UTR_variant	2/2	1	NM_001098201.3	P1
C7orf50	ENST00000397098.8	c.129+33921C>T		intron_variant		1	NM_001318252.2	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26031 AN: 152100 Hom.: 2418 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.179 AC: 48274 AN: 269046 Hom.: 4634 Cov.: 0 AF XY: 0.178 AC XY: 26318 AN XY: 148122

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0655

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.171 AC: 26048 AN: 152218 Hom.: 2421 Cov.: 33 AF XY: 0.171 AC XY: 12758 AN XY: 74442

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0710

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.157

Alfa AF: 0.170 Hom.: 3093

Bravo AF: 0.166

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.80
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3808353; hg19: chr7-1132972;