13-99254970-C-T

Variant names:

Variant summary

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

The NM_001098200.2(GPR18):c.903G>A(p.Met301Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,613,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

GPR18
NM_001098200.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.676

Publications

2 publications found

Variant links:

Genes affected

GPR18 (HGNC:4472): (G protein-coupled receptor 18) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in positive regulation of Rho protein signal transduction and positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to act upstream of or within T cell differentiation; negative regulation of leukocyte chemotaxis; and negative regulation of tumor necrosis factor production. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR18 links:

UBAC2 (HGNC:20486): (UBA domain containing 2) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of retrograde protein transport, ER to cytosol. Acts upstream of or within protein localization to endoplasmic reticulum. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

UBAC2 links:

Genome browser will be placed here

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=0.053548574).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098200.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR18	NM_001098200.2	MANE Select	c.903G>A	p.Met301Ile	missense	Exon 2 of 2	NP_001091670.1	Q14330
UBAC2	NM_001144072.2	MANE Select	c.389+10346C>T		intron	N/A	NP_001137544.1	Q8NBM4-1
GPR18	NM_005292.4		c.903G>A	p.Met301Ile	missense	Exon 3 of 3	NP_005283.1	Q14330

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR18	ENST00000397470.5	TSL:1 MANE Select	c.903G>A	p.Met301Ile	missense	Exon 2 of 2	ENSP00000380610.2	Q14330
GPR18	ENST00000340807.3	TSL:1	c.903G>A	p.Met301Ile	missense	Exon 3 of 3	ENSP00000343428.3	Q14330
GPR18	ENST00000397473.7	TSL:1	c.903G>A	p.Met301Ile	missense	Exon 3 of 3	ENSP00000380613.2	Q14330

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000207

AC:

AN:

251390

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000205

AC:

299

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

149

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000880

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000213

AC:

237

AN:

1111988

Other (OTH)

AF:

0.000232

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000322

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41394

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000755

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000489

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.016

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

M_CAP

Benign

0.0033

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

PhyloP100

0.68

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.090

REVEL

Benign

0.11

Sift

Benign

0.79

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MutPred

0.50

Gain of catalytic residue at M301 (P = 0.0019)

MVP

0.41

MPC

0.087

ClinPred

0.048

GERP RS

5.1

Varity_R

0.17

gMVP

0.63

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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