rs12702047

Positions:

• chr7-1093084-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

C7orf50 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*228G>A		3_prime_UTR_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+34173C>T		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.*228G>A		3_prime_UTR_variant	2/2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+34173C>T		intron_variant		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

GnomAD3 exomes AF: 0.167 AC: 24573 AN: 146768 Hom.: 2238 AF XY: 0.167 AC XY: 13248 AN XY: 79236

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 SAS exome AF: 0.180

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

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0845

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.149

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

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0659

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.137

Alfa AF: 0.155 Hom.: 456

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs12702047; hg19: chr7-1132720;