rs11544331

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3261 hom., cov: 34)

Exomes 𝑓: 0.23 ( 38601 hom. )

Consequence

GPER1
NM_001098201.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.202

Publications

54 publications found

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:

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

CHLSN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GPER1	NM_001098201.3 link	c.47C>T	p.Pro16Leu	missense_variant	Exon 2 of 2	ENST00000397088.4	NP_001091671.1	Q99527A0A024R849
CHLSN	NM_001318252.2 link	c.129+35482G>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.47C>T	p.Pro16Leu	missense_variant	Exon 2 of 2	1	NM_001098201.3	ENSP00000380277.3		Q99527
C7orf50	ENST00000397098.8 link	c.129+35482G>A		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3		Q9BRJ6

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29625

AN:

152154

Hom.:

3256

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.207

AC:

46510

AN:

224812

AF XY:

0.213

show subpopulations

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 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.:

AF XY:

0.229

AC XY:

160295

AN XY:

699136

show subpopulations

African (AFR)

AF:

0.106

AC:

3459

AN:

32500

American (AMR)

AF:

0.196

AC:

8083

AN:

41260

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

6940

AN:

23518

East Asian (EAS)

AF:

0.0269

AC:

1052

AN:

39154

South Asian (SAS)

AF:

0.215

AC:

17105

AN:

79708

European-Finnish (FIN)

AF:

0.191

AC:

9815

AN:

51470

Middle Eastern (MID)

AF:

0.322

AC:

1790

AN:

5558

European-Non Finnish (NFE)

AF:

0.241

AC:

262111

AN:

1086136

Other (OTH)

AF:

0.222

AC:

12960

AN:

58436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12433

24866

37300

49733

62166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8888

17776

26664

35552

44440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.195

AC:

29639

AN:

152272

Hom.:

3261

Cov.:

AF XY:

0.192

AC XY:

14323

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.112

AC:

4640

AN:

41564

American (AMR)

AF:

0.220

AC:

3369

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

1025

AN:

3468

East Asian (EAS)

AF:

0.0263

AC:

136

AN:

5172

South Asian (SAS)

AF:

0.200

AC:

966

AN:

4832

European-Finnish (FIN)

AF:

0.185

AC:

1960

AN:

10618

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16769

AN:

67990

Other (OTH)

AF:

0.203

AC:

430

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1205

2410

3614

4819

6024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.230

Hom.:

11897

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 28, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

BayesDel_noAF

Benign

-0.46

CADD

Benign

1.7

(source)

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

LIST_S2

Benign

0.56

.;T;T;.;.;T

MetaRNN

Benign

0.0042

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.51

N;.;N;N;N;.

PhyloP100

-0.20

PrimateAI

Benign

0.28

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

GERP RS

-0.10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over