Genetic Variant GPER1:c.*179C>T (chr7-1093035-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001098201.3(GPER1):c.*179C>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 0.000135 in 720,674 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: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

GPER1
NM_001098201.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

15 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048771143).

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	Effect	Exon Rank	Protein
GPER1	NM_001098201.3	MANE Select	c.*179C>T	3_prime_UTR	Exon 2 of 2	NP_001091671.1
CHLSN	NM_001318252.2	MANE Select	c.129+34222G>A	intron	N/A	NP_001305181.1
GPER1	NM_001039966.2		c.*179C>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.*179C>T	3_prime_UTR	Exon 2 of 2	ENSP00000380277.3
GPER1	ENST00000297469.3	TSL:1	c.*179C>T	3_prime_UTR	Exon 2 of 2	ENSP00000297469.3
C7orf50	ENST00000397098.8	TSL:1 MANE Select	c.129+34222G>A	intron	N/A	ENSP00000380286.3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000668

AC:

AN:

149792

AF XY:

0.0000496

show subpopulations

Gnomad AFR exome

AF:

0.000732

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:

0.0000348

Gnomad OTH exome

AF:

0.000463

GnomAD4 exome

AF:

0.0000967

AC:

AN:

568482

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

306510

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

15926

American (AMR)

AF:

0.0000289

AC:

AN:

34636

Ashkenazi Jewish (ASJ)

AF:

0.0000499

AC:

AN:

20028

East Asian (EAS)

AF:

0.0000625

AC:

AN:

32000

South Asian (SAS)

AF:

0.0000483

AC:

AN:

62074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45568

Middle Eastern (MID)

AF:

0.000737

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.0000433

AC:

AN:

323394

Other (OTH)

AF:

0.000130

AC:

AN:

30784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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

AF:

0.000276

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.000819

AC:

AN:

41530

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000434

Hom.:

280

ExAC

AF:

0.0000220

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.43

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.91

PhyloP100

-1.5

Sift4G

Pathogenic

0.0

Vest4

0.19

MVP

0.068

ClinPred

0.014

GERP RS

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over