chr7-1091775-C-T

Position:

• chr7-1091775-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098201.3(GPER1):​c.47C>T​(p.Pro16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,570,012 control chromosomes in the GnomAD database, including 41,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (3261 hom., cov: 34)
  • Exomes 𝑓: 0.23 (38601 hom.)
• Consequence: GPER1 NM_001098201.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.202

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041792393).
• BP6: Variant 7-1091775-C-T is Benign according to our data. Variant chr7-1091775-C-T is described in ClinVar as [Benign]. Clinvar id is 1248609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3	c.47C>T	p.Pro16Leu	missense_variant	2/2	ENST00000397088.4	NP_001091671.1
C7orf50	NM_001318252.2	c.129+35482G>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.47C>T	p.Pro16Leu	missense_variant	2/2	1	NM_001098201.3	ENSP00000380277.3
C7orf50	ENST00000397098.8	c.129+35482G>A		intron_variant		1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29625 AN: 152154 Hom.: 3256 Cov.: 34

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.204

GnomAD3 exomes AF: 0.207 AC: 46510 AN: 224812 Hom.: 5467 AF XY: 0.213 AC XY: 25566 AN XY: 120126

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.0240

Gnomad SAS exome AF: 0.210

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.254

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.228 AC: 323315 AN: 1417740 Hom.: 38601 Cov.: 35 AF XY: 0.229 AC XY: 160295 AN XY: 699136

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.0269

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.195 AC: 29639 AN: 152272 Hom.: 3261 Cov.: 34 AF XY: 0.192 AC XY: 14323 AN XY: 74456

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.203

Alfa AF: 0.234 Hom.: 5756

Bravo AF: 0.192

TwinsUK AF: 0.246 AC: 914

ALSPAC AF: 0.225 AC: 868

ESP6500AA AF: 0.115 AC: 507

ESP6500EA AF: 0.245 AC: 2106

ExAC AF: 0.209 AC: 25282

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 28, 2020

This variant is associated with the following publications: (PMID: 31748686) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.7
DANN	Benign	0.72
DEOGEN2	Benign	0.12	T;T;T;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.56	.;T;T;.;.;T
MetaRNN	Benign	0.0042	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.51	N;.;N;N;N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N;D;N;N;N;.
REVEL	Benign	0.099
Sift	Benign	0.17	T;T;T;T;T;.
Sift4G	Benign	0.38	T;T;T;T;T;T
Polyphen		0.0010	B;.;B;B;B;.
Vest4		0.036
MPC		0.42
ClinPred		0.0014	T
GERP RS		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.31

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: rs11544331; hg19: chr7-1131411; COSMIC: COSV52468559; COSMIC: COSV52468559;