NM_001098201.3:c.14C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001098201.3(GPER1):c.14C>T(p.Ser5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0055 in 1,530,888 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 34)

Exomes 𝑓: 0.0055 ( 61 hom. )

Consequence

GPER1
NM_001098201.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0770

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030380487).

BP6

Variant 7-1091742-C-T is Benign according to our data. Variant chr7-1091742-C-T is described in ClinVar as [Benign]. Clinvar id is 770179.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0051 (777/152364) while in subpopulation EAS AF= 0.0242 (125/5174). AF 95% confidence interval is 0.0207. There are 6 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPER1	NM_001098201.3 link	c.14C>T	p.Ser5Phe	missense_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1	Q99527A0A024R849
C7orf50	NM_001318252.2 link	c.129+35515G>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 link	c.14C>T	p.Ser5Phe	missense_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3		Q99527
C7orf50	ENST00000397098.8 link	c.129+35515G>A		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3		Q9BRJ6

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

778

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00573

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00915

AC:

1745

AN:

190654

Hom.:

AF XY:

0.00791

AC XY:

797

AN XY:

100772

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.0360

Gnomad ASJ exome

AF:

0.000454

Gnomad EAS exome

AF:

0.0234

Gnomad SAS exome

AF:

0.000772

Gnomad FIN exome

AF:

0.00169

Gnomad NFE exome

AF:

0.00440

Gnomad OTH exome

AF:

0.00612

GnomAD4 exome

AF:

0.00554

AC:

7643

AN:

1378524

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

3654

AN XY:

676238

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.0320

Gnomad4 ASJ exome

AF:

0.000914

Gnomad4 EAS exome

AF:

0.0254

Gnomad4 SAS exome

AF:

0.000633

Gnomad4 FIN exome

AF:

0.00229

Gnomad4 NFE exome

AF:

0.00474

Gnomad4 OTH exome

AF:

0.00548

GnomAD4 genome

AF:

0.00510

AC:

777

AN:

152364

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00151

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0242

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00573

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00508

Hom.:

Bravo

AF:

0.00694

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00823

AC:

994

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.6

DANN

Uncertain

0.97

DEOGEN2

Benign

0.055

T;T;T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.57

.;T;T;.;.;T

MetaRNN

Benign

0.0030

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.;N;N;N;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.24

N;D;N;N;N;.

REVEL

Benign

0.10

Sift

Uncertain

0.0030

D;D;D;D;D;.

Sift4G

Benign

0.15

T;D;T;T;T;D

Polyphen

0.0

B;.;B;B;B;.

Vest4

0.047

MVP

0.10

MPC

0.45

ClinPred

0.0029

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.042

gMVP

0.53

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