rs2229584

Positions:

• chr1-23874479-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR2	NM_001841.3	c.*56A>G		3_prime_UTR_variant	2/2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.*56A>G		3_prime_UTR_variant	2/2		XP_011538931.1
CNR2	XM_017000261.3	c.*56A>G		3_prime_UTR_variant	3/3		XP_016855750.1
CNR2	XM_047444833.1	c.*56A>G		3_prime_UTR_variant	2/2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.*56A>G		3_prime_UTR_variant	2/2	1	NM_001841.3	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

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.594

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

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.613

Alfa AF: 0.597 Hom.: 10620

Bravo AF: 0.644

Asia WGS AF: 0.630 AC: 2190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.57

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: rs2229584; hg19: chr1-24200969;