Genetic Variant GPER1:p.Arg122Arg (chr7-1092094-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001098201.3(GPER1):c.366G>A(p.Arg122Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GPER1
NM_001098201.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

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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new If you want to explore the variant's impact on the transcript NM_001098201.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP7

Synonymous conserved (PhyloP=2.23 with no splicing effect.

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.366G>A	p.Arg122Arg	synonymous	Exon 2 of 2	NP_001091671.1	Q99527
CHLSN	NM_001318252.2	MANE Select	c.129+35163C>T		intron	N/A	NP_001305181.1	Q9BRJ6
GPER1	NM_001039966.2		c.366G>A	p.Arg122Arg	synonymous	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.366G>A	p.Arg122Arg	synonymous	Exon 2 of 2	ENSP00000380277.3	Q99527
GPER1	ENST00000297469.3	TSL:1	c.366G>A	p.Arg122Arg	synonymous	Exon 2 of 2	ENSP00000297469.3	Q99527
CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.129+35163C>T		intron	N/A	ENSP00000380286.3	Q9BRJ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461556

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.3

(source)

DANN

Benign

0.78

PhyloP100

2.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over