chr2-230910379-C-G

Variant names:

• chr2-230910379-C-G
• rs3749073
• NM_005683.4:c.584G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005683.4(GPR55):​c.584G>C​(p.Gly195Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPR55 NM_005683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 0 publications found

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]

ENSG00000230385 (HGNC:40260):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029150307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR55	NM_005683.4	c.584G>C	p.Gly195Ala	missense_variant	Exon 2 of 2	ENST00000650999.1	NP_005674.2
GPR55	XM_005246952.5	c.584G>C	p.Gly195Ala	missense_variant	Exon 2 of 2		XP_005247009.1
GPR55	XM_011512175.4	c.584G>C	p.Gly195Ala	missense_variant	Exon 2 of 2		XP_011510477.1
GPR55	XM_011512176.3	c.584G>C	p.Gly195Ala	missense_variant	Exon 2 of 2		XP_011510478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR55	ENST00000650999.1	c.584G>C	p.Gly195Ala	missense_variant	Exon 2 of 2		NM_005683.4	ENSP00000498258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461766 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727192

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111904

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.73
DEOGEN2	Benign	0.011	T;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.65	.;T;.;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.029	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N;N;N;.
PhyloP100		0.020
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.7	.;N;N;N
REVEL	Benign	0.064
Sift	Benign	1.0	.;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.049
MutPred		0.31		Loss of stability (P = 0.1593);Loss of stability (P = 0.1593);Loss of stability (P = 0.1593);Loss of stability (P = 0.1593);
MVP		0.19
MPC		0.28
ClinPred		0.032	T
GERP RS		-0.72
Varity_R		0.062
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs3749073; hg19: chr2-231775094;