rs2229586

chr1-23874413-G-Cchr1-23874413-G-T

Variant summary

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

The NM_001841.3(CNR2):c.*122C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,097,694 control chromosomes in the GnomAD database, including 180,412 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 0.59 (26312 hom., cov: 32)
  • Exomes 𝑓: 0.57 (154100 hom.)
• Consequence: CNR2 NM_001841.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNR2	NM_001841.3	c.*122C>G		3_prime_UTR_variant	2/2	ENST00000374472.5
CNR2	XM_011540629.4	c.*122C>G		3_prime_UTR_variant	2/2
CNR2	XM_017000261.3	c.*122C>G		3_prime_UTR_variant	3/3
CNR2	XM_047444833.1	c.*122C>G		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNR2	ENST00000374472.5	c.*122C>G		3_prime_UTR_variant	2/2	1	NM_001841.3	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89455 AN: 151648 Hom.: 26310 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.567 AC: 536798 AN: 945928 Hom.: 154100 Cov.: 12 AF XY: 0.574 AC XY: 274830 AN XY: 478920

Gnomad4 AFR exome AF: 0.606

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.715

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.590 AC: 89488 AN: 151766 Hom.: 26312 Cov.: 32 AF XY: 0.595 AC XY: 44090 AN XY: 74146

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.580

Alfa AF: 0.450 Hom.: 1192

Bravo AF: 0.592

Asia WGS AF: 0.621 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.7
Dann	Benign	0.71

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: rs2229586; hg19: chr1-24200903; COSMIC: COSV65692721;