dbSNP rs1133041: GPER1:c.*199C>T (chr7-1093055-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001505.3(GPER1):c.*199C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 710,968 control chromosomes in the GnomAD database, including 966 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 0.017 ( 94 hom., cov: 33)

Exomes 𝑓: 0.027 ( 872 hom. )

Consequence

GPER1
NM_001505.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015503168).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001505.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GPER1	NM_001098201.3	MANE Select	c.*199C>T	3_prime_UTR	Exon 2 of 2	NP_001091671.1
CHLSN	NM_001318252.2	MANE Select	c.129+34202G>A	intron	N/A	NP_001305181.1
GPER1	NM_001039966.2		c.*199C>T	3_prime_UTR	Exon 3 of 3	NP_001035055.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GPER1	ENST00000397088.4	TSL:1 MANE Select	c.*199C>T	3_prime_UTR	Exon 2 of 2	ENSP00000380277.3
GPER1	ENST00000297469.3	TSL:1	c.*199C>T	3_prime_UTR	Exon 2 of 2	ENSP00000297469.3
CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.129+34202G>A	intron	N/A	ENSP00000380286.3

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2594

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0296

AC:

4411

AN:

148842

AF XY:

0.0281

show subpopulations

Gnomad AFR exome

AF:

0.00280

Gnomad AMR exome

AF:

0.0389

Gnomad ASJ exome

AF:

0.0287

Gnomad EAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.0280

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.0242

GnomAD4 exome

AF:

0.0270

AC:

15068

AN:

558678

Hom.:

872

Cov.:

AF XY:

0.0260

AC XY:

7855

AN XY:

301772

show subpopulations

African (AFR)

AF:

0.00267

AC:

AN:

15758

American (AMR)

AF:

0.0355

AC:

1224

AN:

34496

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

598

AN:

19908

East Asian (EAS)

AF:

0.209

AC:

6627

AN:

31708

South Asian (SAS)

AF:

0.00932

AC:

577

AN:

61934

European-Finnish (FIN)

AF:

0.0284

AC:

1250

AN:

44042

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.0127

AC:

4032

AN:

316332

Other (OTH)

AF:

0.0213

AC:

649

AN:

30440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

702

1403

2105

2806

3508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.0170

AC:

2590

AN:

152290

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1434

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00325

AC:

135

AN:

41570

American (AMR)

AF:

0.0157

AC:

240

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3472

East Asian (EAS)

AF:

0.169

AC:

872

AN:

5162

South Asian (SAS)

AF:

0.0118

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0315

AC:

334

AN:

10620

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0119

AC:

810

AN:

68018

Other (OTH)

AF:

0.0142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

123

246

368

491

614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0159

Hom.:

143

Bravo

AF:

0.0178

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00908

AC:

ExAC

AF:

0.0103

AC:

409

Asia WGS

AF:

0.0800

AC:

276

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.9

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.014

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

PhyloP100

-0.17

Sift4G

Pathogenic

0.0

Vest4

0.064

ClinPred

0.00078

GERP RS

-1.1

Mutation Taster

=100/0

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over