7-1093669-C-G

Variant names:

• chr7-1093669-C-G
• rs1133043
• NM_001098201.3:c.*813C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098201.3(GPER1):​c.*813C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 469,890 control chromosomes in the GnomAD database, including 93,478 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 0.65 (32780 hom., cov: 34)
  • Exomes 𝑓: 0.61 (60698 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 25 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=1.6484207E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*813C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+33588G>C		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.*813C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+33588G>C		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98932 AN: 152076 Hom.: 32745 Cov.: 34

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.625

GnomAD2 exomes AF: 0.607 AC: 92084 AN: 151652 AF XY: 0.604

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.627

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.381

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.599

GnomAD4 exome AF: 0.615 AC: 195369 AN: 317696 Hom.: 60698 Cov.: 0 AF XY: 0.611 AC XY: 109509 AN XY: 179260

African (AFR) AF: 0.752 AC: 6475 AN: 8612

American (AMR) AF: 0.629 AC: 17142 AN: 27270

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 6810 AN: 10786

East Asian (EAS) AF: 0.409 AC: 3737 AN: 9148

South Asian (SAS) AF: 0.580 AC: 34616 AN: 59728

European-Finnish (FIN) AF: 0.645 AC: 17429 AN: 27042

Middle Eastern (MID) AF: 0.620 AC: 1721 AN: 2778

European-Non Finnish (NFE) AF: 0.624 AC: 98658 AN: 158026

Other (OTH) AF: 0.614 AC: 8781 AN: 14306

GnomAD4 genome AF: 0.651 AC: 99009 AN: 152194 Hom.: 32780 Cov.: 34 AF XY: 0.647 AC XY: 48124 AN XY: 74404

African (AFR) AF: 0.751 AC: 31206 AN: 41540

American (AMR) AF: 0.615 AC: 9413 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2167 AN: 3470

East Asian (EAS) AF: 0.408 AC: 2108 AN: 5162

South Asian (SAS) AF: 0.556 AC: 2687 AN: 4830

European-Finnish (FIN) AF: 0.641 AC: 6788 AN: 10592

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42549 AN: 67990

Other (OTH) AF: 0.622 AC: 1314 AN: 2112

Alfa AF: 0.588 Hom.: 3343

Bravo AF: 0.651

TwinsUK AF: 0.616 AC: 2283

ALSPAC AF: 0.619 AC: 2385

ExAC AF: 0.583 AC: 12060

Asia WGS AF: 0.508 AC: 1765 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.43
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0000016	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.8
Vest4		0.057
ClinPred		0.0043	T
GERP RS		-0.41
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: rs1133043; hg19: chr7-1133305;