rs2229584

Variant names:

• chr1-23874479-T-C
• rs2229584
• NM_001841.3:c.*56A>G

Variant summary

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

The NM_001841.3(CNR2):​c.*56A>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 0.593 in 1,547,208 control chromosomes in the GnomAD database, including 275,092 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 (30809 hom., cov: 31)
  • Exomes 𝑓: 0.59 (244283 hom.)
• Consequence: CNR2 NM_001841.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	NM_001841.3	MANE Select	c.*56A>G		3_prime_UTR	Exon 2 of 2	NP_001832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	ENST00000374472.5	TSL:1 MANE Select	c.*56A>G		3_prime_UTR	Exon 2 of 2	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96006 AN: 151504 Hom.: 30799 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.589 AC: 821360 AN: 1395586 Hom.: 244283 Cov.: 26 AF XY: 0.592 AC XY: 409121 AN XY: 690980

African (AFR) AF: 0.766 AC: 24152 AN: 31536

American (AMR) AF: 0.689 AC: 27136 AN: 39362

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 13076 AN: 22616

East Asian (EAS) AF: 0.570 AC: 22385 AN: 39294

South Asian (SAS) AF: 0.720 AC: 56267 AN: 78166

European-Finnish (FIN) AF: 0.577 AC: 26432 AN: 45828

Middle Eastern (MID) AF: 0.712 AC: 3887 AN: 5458

European-Non Finnish (NFE) AF: 0.571 AC: 613713 AN: 1075594

Other (OTH) AF: 0.594 AC: 34312 AN: 57732

GnomAD4 genome AF: 0.634 AC: 96058 AN: 151622 Hom.: 30809 Cov.: 31 AF XY: 0.636 AC XY: 47138 AN XY: 74082

African (AFR) AF: 0.755 AC: 31228 AN: 41338

American (AMR) AF: 0.641 AC: 9763 AN: 15238

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

East Asian (EAS) AF: 0.525 AC: 2700 AN: 5144

South Asian (SAS) AF: 0.714 AC: 3437 AN: 4816

European-Finnish (FIN) AF: 0.573 AC: 6004 AN: 10484

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

European-Non Finnish (NFE) AF: 0.574 AC: 38940 AN: 67842

Other (OTH) AF: 0.613 AC: 1289 AN: 2104

Alfa AF: 0.600 Hom.: 16809

Bravo AF: 0.644

Asia WGS AF: 0.630 AC: 2190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		-0.46
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: rs2229584; hg19: chr1-24200969;