rs2502992

Variant names:

• chr1-23875429-T-C
• rs2502992
• NM_001841.3:c.189A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-23875429-T-C
• chr1-23875429-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001841.3(CNR2):​c.189A>G​(p.Gln63Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,440 control chromosomes in the GnomAD database, including 286,874 homozygotes. 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 0.63 (30835 hom., cov: 33)
  • Exomes 𝑓: 0.59 (256039 hom.)
• Consequence: CNR2 NM_001841.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 17 publications found

Genes affected

CNR2 (HGNC:2160): (cannabinoid receptor 2) The cannabinoid delta-9-tetrahydrocannabinol is the principal psychoactive ingredient of marijuana. The proteins encoded by this gene and the cannabinoid receptor 1 (brain) (CNR1) gene have the characteristics of a guanine nucleotide-binding protein (G-protein)-coupled receptor for cannabinoids. They inhibit adenylate cyclase activity in a dose-dependent, stereoselective, and pertussis toxin-sensitive manner. These proteins have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. The cannabinoid receptors are members of family 1 of the G-protein-coupled receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=0.305 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001841.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	NM_001841.3	MANE Select	c.189A>G	p.Gln63Gln	synonymous	Exon 2 of 2	NP_001832.1	P34972

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	ENST00000374472.5	TSL:1 MANE Select	c.189A>G	p.Gln63Gln	synonymous	Exon 2 of 2	ENSP00000363596.4	P34972

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96097 AN: 151580 Hom.: 30825 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.618

GnomAD2 exomes AF: 0.617 AC: 154378 AN: 250348 AF XY: 0.617

Gnomad AFR exome AF: 0.762

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.589 AC: 861490 AN: 1461742 Hom.: 256039 Cov.: 68 AF XY: 0.593 AC XY: 430996 AN XY: 727140

African (AFR) AF: 0.766 AC: 25631 AN: 33480

American (AMR) AF: 0.680 AC: 30385 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 14983 AN: 26136

East Asian (EAS) AF: 0.569 AC: 22584 AN: 39688

South Asian (SAS) AF: 0.719 AC: 62044 AN: 86256

European-Finnish (FIN) AF: 0.574 AC: 30621 AN: 53392

Middle Eastern (MID) AF: 0.710 AC: 4092 AN: 5766

European-Non Finnish (NFE) AF: 0.571 AC: 635306 AN: 1111928

Other (OTH) AF: 0.594 AC: 35844 AN: 60388

GnomAD4 genome AF: 0.634 AC: 96149 AN: 151698 Hom.: 30835 Cov.: 33 AF XY: 0.637 AC XY: 47201 AN XY: 74102

African (AFR) AF: 0.756 AC: 31264 AN: 41374

American (AMR) AF: 0.641 AC: 9779 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2011 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2680 AN: 5116

South Asian (SAS) AF: 0.713 AC: 3439 AN: 4822

European-Finnish (FIN) AF: 0.575 AC: 6030 AN: 10496

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 38956 AN: 67856

Other (OTH) AF: 0.612 AC: 1293 AN: 2112

Alfa AF: 0.599 Hom.: 17833

Bravo AF: 0.644

Asia WGS AF: 0.630 AC: 2190 AN: 3478

EpiCase AF: 0.578

EpiControl AF: 0.590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.40
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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: rs2502992; hg19: chr1-24201919; COSMIC: COSV65692454;