1-23874619-C-T

Variant names:

• chr1-23874619-C-T
• rs2229580
• NM_001841.3:c.999G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001841.3(CNR2):​c.999G>A​(p.Pro333Pro) 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 1,613,664 control chromosomes in the GnomAD database, including 287,068 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 (30996 hom., cov: 32)
  • Exomes 𝑓: 0.59 (256072 hom.)
• Consequence: CNR2 NM_001841.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-2.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	NM_001841.3	MANE Select	c.999G>A	p.Pro333Pro	synonymous	Exon 2 of 2	NP_001832.1	P34972

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	ENST00000374472.5	TSL:1 MANE Select	c.999G>A	p.Pro333Pro	synonymous	Exon 2 of 2	ENSP00000363596.4	P34972

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96373 AN: 151846 Hom.: 30986 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.619

GnomAD2 exomes AF: 0.617 AC: 155217 AN: 251464 AF XY: 0.617

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.529

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.574

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.589 AC: 861490 AN: 1461700 Hom.: 256072 Cov.: 56 AF XY: 0.593 AC XY: 431017 AN XY: 727172

African (AFR) AF: 0.766 AC: 25628 AN: 33474

American (AMR) AF: 0.680 AC: 30399 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 14980 AN: 26130

East Asian (EAS) AF: 0.569 AC: 22583 AN: 39692

South Asian (SAS) AF: 0.719 AC: 62041 AN: 86252

European-Finnish (FIN) AF: 0.574 AC: 30640 AN: 53414

Middle Eastern (MID) AF: 0.709 AC: 4091 AN: 5768

European-Non Finnish (NFE) AF: 0.571 AC: 635291 AN: 1111856

Other (OTH) AF: 0.593 AC: 35837 AN: 60390

GnomAD4 genome AF: 0.635 AC: 96425 AN: 151964 Hom.: 30996 Cov.: 32 AF XY: 0.638 AC XY: 47353 AN XY: 74238

African (AFR) AF: 0.756 AC: 31363 AN: 41480

American (AMR) AF: 0.642 AC: 9783 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2704 AN: 5158

South Asian (SAS) AF: 0.713 AC: 3436 AN: 4816

European-Finnish (FIN) AF: 0.578 AC: 6098 AN: 10550

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

European-Non Finnish (NFE) AF: 0.575 AC: 39039 AN: 67936

Other (OTH) AF: 0.613 AC: 1291 AN: 2106

Alfa AF: 0.600 Hom.: 18079

Bravo AF: 0.644

Asia WGS AF: 0.630 AC: 2193 AN: 3478

EpiCase AF: 0.578

EpiControl AF: 0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.051
DANN	Benign	0.40
PhyloP100		-2.9
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: rs2229580; hg19: chr1-24201109; COSMIC: COSV65692441;