rs1133041

Variant names:

• chr7-1093055-C-T
• rs1133041
• NM_001098201.3:c.*199C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 (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 rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*199C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+34202G>A		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.*199C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+34202G>A		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

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

GnomAD2 exomes AF: 0.0296 AC: 4411 AN: 148842 AF XY: 0.0281

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 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

African (AFR) AF: 0.00267 AC: 42 AN: 15758

American (AMR) AF: 0.0355 AC: 1224 AN: 34496

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 598 AN: 19908

East Asian (EAS) AF: 0.209 AC: 6627 AN: 31708

South Asian (SAS) AF: 0.00932 AC: 577 AN: 61934

European-Finnish (FIN) AF: 0.0284 AC: 1250 AN: 44042

Middle Eastern (MID) AF: 0.0170 AC: 69 AN: 4060

European-Non Finnish (NFE) AF: 0.0127 AC: 4032 AN: 316332

Other (OTH) AF: 0.0213 AC: 649 AN: 30440

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

African (AFR) AF: 0.00325 AC: 135 AN: 41570

American (AMR) AF: 0.0157 AC: 240 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3472

East Asian (EAS) AF: 0.169 AC: 872 AN: 5162

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4828

European-Finnish (FIN) AF: 0.0315 AC: 334 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 810 AN: 68018

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.0159 Hom.: 143

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
PhyloP100		-0.17
Sift4G	Pathogenic	0.0	D;D
Vest4		0.064
ClinPred		0.00078	T
GERP RS		-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: rs1133041; hg19: chr7-1132691; COSMIC: COSV52469030; COSMIC: COSV52469030;