rs3749073

chr2-230910379-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (3054 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10417 hom.)
• Consequence: GPR55 NM_005683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GPR55	NM_005683.4	c.584G>T	p.Gly195Val	missense_variant	2/2	ENST00000650999.1
GPR55	XM_005246952.5	c.584G>T	p.Gly195Val	missense_variant	2/2
GPR55	XM_011512175.4	c.584G>T	p.Gly195Val	missense_variant	2/2
GPR55	XM_011512176.3	c.584G>T	p.Gly195Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR55	ENST00000650999.1	c.584G>T	p.Gly195Val	missense_variant	2/2		NM_005683.4	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25136 AN: 151894 Hom.: 3044 Cov.: 32

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

GnomAD3 exomes AF: 0.119 AC: 29881 AN: 251412 Hom.: 2591 AF XY: 0.119 AC XY: 16237 AN XY: 135882

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 SAS exome AF: 0.197

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.: 34 AF XY: 0.110 AC XY: 80168 AN XY: 727158

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.0551

Gnomad4 ASJ exome AF: 0.0680

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.0986

Gnomad4 NFE exome AF: 0.0953

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.166 AC: 25186 AN: 152012 Hom.: 3054 Cov.: 32 AF XY: 0.161 AC XY: 11995 AN XY: 74312

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.0956

Gnomad4 OTH AF: 0.149

Alfa AF: 0.108 Hom.: 2365

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	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	6.4
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	N
MetaRNN	Benign	0.0025	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N;N;N;.
MutationTaster	Benign	0.034	P;P
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.026	B;B;B;.
Vest4		0.059
MPC		0.33
ClinPred		0.0066	T
GERP RS		-0.72
Varity_R		0.087

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

LitVar

Other links and lift over

dbSNP: rs3749073; hg19: chr2-231775094; COSMIC: COSV67407042; COSMIC: COSV67407042;