Genetic Variant GPER1:c.-327G>A (chr7-1087240-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000297469.3(GPER1):c.-327G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,292 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.046 ( 212 hom., cov: 33)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

GPER1
ENST00000297469.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.442

Publications

11 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHLSN	NM_001318252.2 link	c.129+40017C>T		intron_variant	Intron 2 of 4	ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7orf50	ENST00000397098.8 link	c.129+40017C>T		intron_variant	Intron 2 of 4	1	NM_001318252.2	ENSP00000380286.3		Q9BRJ6

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6928

AN:

152164

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.0674

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.0783

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0304

Gnomad OTH

AF:

0.0407

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0455

AC:

6930

AN:

152280

Hom.:

212

Cov.:

AF XY:

0.0460

AC XY:

3425

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0665

AC:

2762

AN:

41556

American (AMR)

AF:

0.0455

AC:

696

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3470

East Asian (EAS)

AF:

0.0676

AC:

350

AN:

5180

South Asian (SAS)

AF:

0.00560

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0783

AC:

831

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0304

AC:

2068

AN:

68024

Other (OTH)

AF:

0.0398

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

346

692

1038

1384

1730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0328

Hom.:

138

Bravo

AF:

0.0443

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

(source)

DANN

Benign

0.73

PhyloP100

-0.44

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr7-1087240-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over