Variant chr7-1092552-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001098201.3(GPER1):c.824A>G(p.Glu275Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GPER1
NM_001098201.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.65

Variant links:

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]

GPER1 links:

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

C7orf50 links:

C7orf50 (HGNC:):

C7orf50 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPER1	NM_001098201.3 linkuse as main transcript	c.824A>G	p.Glu275Gly	missense_variant	2/2	ENST00000397088.4	NP_001091671.1	Q99527A0A024R849
C7orf50	NM_001318252.2 linkuse as main transcript	c.129+34705T>C		intron_variant		ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPER1	ENST00000397088.4 linkuse as main transcript	c.824A>G	p.Glu275Gly	missense_variant	2/2	1	NM_001098201.3	ENSP00000380277.3		Q99527
C7orf50	ENST00000397098.8 linkuse as main transcript	c.129+34705T>C		intron_variant		1	NM_001318252.2	ENSP00000380286.3		Q9BRJ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247810

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1457470

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.824A>G (p.E275G) alteration is located in exon 3 (coding exon 1) of the GPER1 gene. This alteration results from a A to G substitution at nucleotide position 824, causing the glutamic acid (E) at amino acid position 275 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;T;T;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

.;T;.;.;T

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.82

D;D;D;D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.2

L;L;L;L;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.1

N;N;N;N;.

REVEL

Uncertain

0.56

Sift

Benign

0.069

T;T;T;T;.

Sift4G

Benign

0.45

T;T;T;T;D

Polyphen

1.0

D;D;D;D;.

Vest4

0.73

MutPred

0.63

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.63

MPC

1.4

ClinPred

0.74

GERP RS

5.4

Varity_R

0.49

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over