rs2502992

Positions:

• chr1-23875429-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001841.3(CNR2):​c.189A>G​(p.Gln63=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR2	NM_001841.3	c.189A>G	p.Gln63=	synonymous_variant	2/2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.189A>G	p.Gln63=	synonymous_variant	2/2		XP_011538931.1
CNR2	XM_017000261.3	c.189A>G	p.Gln63=	synonymous_variant	3/3		XP_016855750.1
CNR2	XM_047444833.1	c.189A>G	p.Gln63=	synonymous_variant	2/2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.189A>G	p.Gln63=	synonymous_variant	2/2	1	NM_001841.3	ENSP00000363596	P1

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

GnomAD3 exomes AF: 0.617 AC: 154378 AN: 250348 Hom.: 48313 AF XY: 0.617 AC XY: 83701 AN XY: 135618

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 SAS exome AF: 0.717

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

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.569

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.594

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

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.612

Alfa AF: 0.599 Hom.: 14004

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

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