rs2229583

Variant names:

• chr1-23874493-C-T
• rs2229583
• NM_001841.3:c.*42G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001841.3(CNR2):​c.*42G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,569,648 control chromosomes in the GnomAD database, including 281,539 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 0.64 (31666 hom., cov: 31)
  • Exomes 𝑓: 0.59 (249873 hom.)
• Consequence: CNR2 NM_001841.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR2	NM_001841.3	c.*42G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.*42G>A		3_prime_UTR_variant	Exon 2 of 2		XP_011538931.1
CNR2	XM_017000261.3	c.*42G>A		3_prime_UTR_variant	Exon 3 of 3		XP_016855750.1
CNR2	XM_047444833.1	c.*42G>A		3_prime_UTR_variant	Exon 2 of 2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.*42G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97117 AN: 151520 Hom.: 31643 Cov.: 31

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.624

GnomAD2 exomes AF: 0.623 AC: 140785 AN: 226034 AF XY: 0.623

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.695

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.530

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.614

GnomAD4 exome AF: 0.590 AC: 837018 AN: 1418010 Hom.: 249873 Cov.: 30 AF XY: 0.594 AC XY: 417194 AN XY: 702682

African (AFR) AF: 0.790 AC: 25313 AN: 32054

American (AMR) AF: 0.688 AC: 27979 AN: 40678

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 13772 AN: 23806

East Asian (EAS) AF: 0.569 AC: 22409 AN: 39356

South Asian (SAS) AF: 0.721 AC: 58851 AN: 81600

European-Finnish (FIN) AF: 0.578 AC: 28236 AN: 48856

Middle Eastern (MID) AF: 0.713 AC: 3967 AN: 5566

European-Non Finnish (NFE) AF: 0.572 AC: 621577 AN: 1087594

Other (OTH) AF: 0.597 AC: 34914 AN: 58500

GnomAD4 genome AF: 0.641 AC: 97192 AN: 151638 Hom.: 31666 Cov.: 31 AF XY: 0.644 AC XY: 47698 AN XY: 74088

African (AFR) AF: 0.781 AC: 32271 AN: 41338

American (AMR) AF: 0.644 AC: 9831 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2005 AN: 3462

East Asian (EAS) AF: 0.525 AC: 2700 AN: 5142

South Asian (SAS) AF: 0.713 AC: 3436 AN: 4818

European-Finnish (FIN) AF: 0.574 AC: 6015 AN: 10484

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

European-Non Finnish (NFE) AF: 0.574 AC: 38936 AN: 67824

Other (OTH) AF: 0.618 AC: 1301 AN: 2106

Alfa AF: 0.612 Hom.: 9051

Bravo AF: 0.652

Asia WGS AF: 0.632 AC: 2198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.55
DANN	Benign	0.40
PhyloP100		-0.0040
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: rs2229583; hg19: chr1-24200983;