rs1133041

Positions:

• chr7-1093055-C-T

Variant summary

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

The NM_001098201.3(GPER1):​c.*199C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 710,968 control chromosomes in the GnomAD database, including 966 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 0.017 (94 hom., cov: 33)
  • Exomes 𝑓: 0.027 (872 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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 (MetaRNN=0.0015503168).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*199C>T		3_prime_UTR_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+34202G>A		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4	c.*199C>T		3_prime_UTR_variant	2/2	1	NM_001098201.3	ENSP00000380277	P1
C7orf50	ENST00000397098.8	c.129+34202G>A		intron_variant		1	NM_001318252.2	ENSP00000380286	P1

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2594 AN: 152172 Hom.: 94 Cov.: 33

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.0296 AC: 4411 AN: 148842 Hom.: 213 AF XY: 0.0281 AC XY: 2252 AN XY: 80260

Gnomad AFR exome AF: 0.00280

Gnomad AMR exome AF: 0.0389

Gnomad ASJ exome AF: 0.0287

Gnomad EAS exome AF: 0.171

Gnomad SAS exome AF: 0.00910

Gnomad FIN exome AF: 0.0280

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.0242

GnomAD4 exome AF: 0.0270 AC: 15068 AN: 558678 Hom.: 872 Cov.: 4 AF XY: 0.0260 AC XY: 7855 AN XY: 301772

Gnomad4 AFR exome AF: 0.00267

Gnomad4 AMR exome AF: 0.0355

Gnomad4 ASJ exome AF: 0.0300

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.00932

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0213

GnomAD4 genome AF: 0.0170 AC: 2590 AN: 152290 Hom.: 94 Cov.: 33 AF XY: 0.0193 AC XY: 1434 AN XY: 74460

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0139 Hom.: 22

Bravo AF: 0.0178

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00908 AC: 35

ExAC AF: 0.0103 AC: 409

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.70
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.24	T;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
Sift4G	Pathogenic	0.0	D;D
Vest4		0.064
ClinPred		0.00078	T
GERP RS		-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: rs1133041; hg19: chr7-1132691; COSMIC: COSV52469030; COSMIC: COSV52469030;