Genetic Variant NM_005683.4:c.584G>T (chr2-230910379-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005683.4(GPR55):c.584G>T(p.Gly195Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,682 control chromosomes in the GnomAD database, including 13,471 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 3054 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10417 hom. )

Consequence

GPR55
NM_005683.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200

Publications

26 publications found

Variant links:

Genes affected

GPR55 (HGNC:4511): (G protein-coupled receptor 55) This gene belongs to the G-protein-coupled receptor superfamily. The encoded integral membrane protein is a likely cannabinoid receptor. It may be involved in several physiological and pathological processes by activating a variety of signal transduction pathways. [provided by RefSeq, Aug 2013]

GPR55 links:

ENSG00000230385 (HGNC:40260):

ENSG00000230385 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=0.0025137067).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR55	NM_005683.4 link	c.584G>T	p.Gly195Val	missense_variant	Exon 2 of 2	ENST00000650999.1	NP_005674.2	Q9Y2T6A8K858
GPR55	XM_005246952.5 link	c.584G>T	p.Gly195Val	missense_variant	Exon 2 of 2		XP_005247009.1	Q9Y2T6A8K858
GPR55	XM_011512175.4 link	c.584G>T	p.Gly195Val	missense_variant	Exon 2 of 2		XP_011510477.1	Q9Y2T6A8K858
GPR55	XM_011512176.3 link	c.584G>T	p.Gly195Val	missense_variant	Exon 2 of 2		XP_011510478.1	Q9Y2T6A8K858

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR55	ENST00000650999.1 link	c.584G>T	p.Gly195Val	missense_variant	Exon 2 of 2		NM_005683.4	ENSP00000498258.1		Q9Y2T6

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25136

AN:

151894

Hom.:

3044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0869

Gnomad ASJ

AF:

0.0660

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0939

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0956

Gnomad OTH

AF:

0.147

GnomAD2 exomes

AF:

0.119

AC:

29881

AN:

251412

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.0504

Gnomad ASJ exome

AF:

0.0705

Gnomad EAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.0953

Gnomad NFE exome

AF:

0.0939

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.108

AC:

158135

AN:

1461670

Hom.:

10417

Cov.:

AF XY:

0.110

AC XY:

80168

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.351

AC:

11744

AN:

33476

American (AMR)

AF:

0.0551

AC:

2466

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0680

AC:

1778

AN:

26136

East Asian (EAS)

AF:

0.155

AC:

6171

AN:

39696

South Asian (SAS)

AF:

0.191

AC:

16479

AN:

86250

European-Finnish (FIN)

AF:

0.0986

AC:

5266

AN:

53418

Middle Eastern (MID)

AF:

0.139

AC:

801

AN:

5768

European-Non Finnish (NFE)

AF:

0.0953

AC:

105968

AN:

1111820

Other (OTH)

AF:

0.124

AC:

7462

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

8296

16592

24889

33185

41481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4120

8240

12360

16480

20600

<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:

0.166

AC:

25186

AN:

152012

Hom.:

3054

Cov.:

AF XY:

0.161

AC XY:

11995

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.339

AC:

14030

AN:

41416

American (AMR)

AF:

0.0868

AC:

1327

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0660

AC:

229

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

724

AN:

5162

South Asian (SAS)

AF:

0.194

AC:

931

AN:

4794

European-Finnish (FIN)

AF:

0.0939

AC:

994

AN:

10590

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0956

AC:

6501

AN:

67970

Other (OTH)

AF:

0.149

AC:

315

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

946

1892

2838

3784

4730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.114

Hom.:

5338

Bravo

AF:

0.170

TwinsUK

AF:

0.101

AC:

374

ALSPAC

AF:

0.0939

AC:

362

ESP6500AA

AF:

0.329

AC:

1451

ESP6500EA

AF:

0.0928

AC:

798

ExAC

AF:

0.128

AC:

15504

Asia WGS

AF:

0.233

AC:

809

AN:

3478

EpiCase

AF:

0.0985

EpiControl

AF:

0.0910

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.4

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.011

T;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.63

.;T;.;T

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

N;N;N;.

PhyloP100

0.020

PrimateAI

Benign

0.27

PROVEAN

Benign

1.0

.;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.097

.;T;T;T

Sift4G

Benign

0.15

T;T;T;T

Polyphen

0.026

B;B;B;.

Vest4

0.059

MPC

0.33

ClinPred

0.0066

GERP RS

-0.72

Varity_R

0.087

Mutation Taster

=93/7

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over