7-1093035-C-G

Variant names:

• chr7-1093035-C-G
• rs4266553
• NM_001098201.3:c.*179C>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.*179C>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 0.108 in 720,544 control chromosomes in the GnomAD database, including 4,595 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 0.11 (923 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3672 hom.)
• Consequence: GPER1 NM_001098201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 15 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=0.0017130375).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.*179C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1
CHLSN	NM_001318252.2	c.129+34222G>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.*179C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+34222G>C		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15990 AN: 152042 Hom.: 921 Cov.: 32

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.106 AC: 15928 AN: 149792 AF XY: 0.109

Gnomad AFR exome AF: 0.0963

Gnomad AMR exome AF: 0.0879

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0439

Gnomad FIN exome AF: 0.0868

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.109 AC: 61745 AN: 568386 Hom.: 3672 Cov.: 5 AF XY: 0.110 AC XY: 33805 AN XY: 306454

African (AFR) AF: 0.0986 AC: 1570 AN: 15926

American (AMR) AF: 0.0895 AC: 3099 AN: 34636

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 2859 AN: 20022

East Asian (EAS) AF: 0.0401 AC: 1282 AN: 31990

South Asian (SAS) AF: 0.130 AC: 8090 AN: 62074

European-Finnish (FIN) AF: 0.0839 AC: 3822 AN: 45548

Middle Eastern (MID) AF: 0.0722 AC: 294 AN: 4072

European-Non Finnish (NFE) AF: 0.115 AC: 37334 AN: 323338

Other (OTH) AF: 0.110 AC: 3395 AN: 30780

GnomAD4 genome AF: 0.105 AC: 15995 AN: 152158 Hom.: 923 Cov.: 32 AF XY: 0.103 AC XY: 7634 AN XY: 74378

African (AFR) AF: 0.0976 AC: 4053 AN: 41518

American (AMR) AF: 0.100 AC: 1536 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.0542 AC: 280 AN: 5168

South Asian (SAS) AF: 0.125 AC: 603 AN: 4814

European-Finnish (FIN) AF: 0.0808 AC: 858 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7802 AN: 67978

Other (OTH) AF: 0.109 AC: 229 AN: 2110

Alfa AF: 0.0907 Hom.: 280

Bravo AF: 0.104

TwinsUK AF: 0.121 AC: 448

ALSPAC AF: 0.127 AC: 488

ExAC AF: 0.0632 AC: 2876

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.55
DANN	Benign	0.60
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.32	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.5
Sift4G	Pathogenic	0.0	D;D
Vest4		0.12
ClinPred		0.0026	T
GERP RS		0.28
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: rs4266553; hg19: chr7-1132671;