7-1093336-G-A

Variant names:

• chr7-1093336-G-A
• rs3808353
• NM_001098201.3:c.*480G>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.*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
• Publications: 12 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=-0.89).
• 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 rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*480G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+33921C>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.*480G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+33921C>T		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

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

African (AFR) AF: 0.159 AC: 1216 AN: 7664

American (AMR) AF: 0.225 AC: 5278 AN: 23438

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 804 AN: 7192

East Asian (EAS) AF: 0.0655 AC: 573 AN: 8748

South Asian (SAS) AF: 0.181 AC: 9243 AN: 50928

European-Finnish (FIN) AF: 0.235 AC: 5848 AN: 24910

Middle Eastern (MID) AF: 0.127 AC: 305 AN: 2402

European-Non Finnish (NFE) AF: 0.175 AC: 23060 AN: 131662

Other (OTH) AF: 0.161 AC: 1947 AN: 12102

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

African (AFR) AF: 0.163 AC: 6777 AN: 41540

American (AMR) AF: 0.171 AC: 2609 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3466

East Asian (EAS) AF: 0.0710 AC: 368 AN: 5186

South Asian (SAS) AF: 0.180 AC: 869 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12109 AN: 67992

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.172 Hom.: 5674

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
PhyloP100		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3808353; hg19: chr7-1132972;