Genetic Variant GPER1:p.Pro36Gln (chr7-1091835-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098201.3(GPER1):c.107C>A(p.Pro36Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GPER1
NM_001098201.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.415

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062164277).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPER1	NM_001098201.3	MANE Select	c.107C>A	p.Pro36Gln	missense	Exon 2 of 2	NP_001091671.1	Q99527
CHLSN	NM_001318252.2	MANE Select	c.129+35422G>T		intron	N/A	NP_001305181.1	Q9BRJ6
GPER1	NM_001039966.2		c.107C>A	p.Pro36Gln	missense	Exon 3 of 3	NP_001035055.1	Q99527

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPER1	ENST00000397088.4	TSL:1 MANE Select	c.107C>A	p.Pro36Gln	missense	Exon 2 of 2	ENSP00000380277.3	Q99527
GPER1	ENST00000297469.3	TSL:1	c.107C>A	p.Pro36Gln	missense	Exon 2 of 2	ENSP00000297469.3	Q99527
CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.129+35422G>T		intron	N/A	ENSP00000380286.3	Q9BRJ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

249032

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455488

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722746

African (AFR)

AF:

0.00

AC:

AN:

33386

American (AMR)

AF:

0.00

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.00

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107288

Other (OTH)

AF:

0.00

AC:

AN:

60118

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.019

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.052

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.43

M_CAP

Benign

0.014

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

PhyloP100

-0.41

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.24

REVEL

Benign

0.082

Sift

Benign

0.57

Sift4G

Benign

0.72

Polyphen

0.089

Vest4

0.071

MutPred

0.36

Loss of glycosylation at S34 (P = 0.0717)

MVP

0.29

MPC

0.38

ClinPred

0.034

GERP RS

-2.3

Varity_R

0.024

gMVP

0.30

Mutation Taster

=96/4

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over