1-23874413-G-C

Variant names:

• chr1-23874413-G-C
• rs2229586
• NM_001841.3:c.*122C>G

Variant summary

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

The ENST00000374472.5(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 ENST00000374472.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374472.5. 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.*122C>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.*122C>G		3_prime_UTR	Exon 2 of 2	ENSP00000363596.4

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

African (AFR) AF: 0.606 AC: 13000 AN: 21446

American (AMR) AF: 0.658 AC: 18678 AN: 28384

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 9808 AN: 17404

East Asian (EAS) AF: 0.570 AC: 21102 AN: 37022

South Asian (SAS) AF: 0.715 AC: 43285 AN: 60522

European-Finnish (FIN) AF: 0.566 AC: 19572 AN: 34608

Middle Eastern (MID) AF: 0.686 AC: 2401 AN: 3500

European-Non Finnish (NFE) AF: 0.549 AC: 384733 AN: 700486

Other (OTH) AF: 0.569 AC: 24219 AN: 42556

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

African (AFR) AF: 0.608 AC: 25183 AN: 41410

American (AMR) AF: 0.618 AC: 9428 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2000 AN: 3462

East Asian (EAS) AF: 0.522 AC: 2684 AN: 5140

South Asian (SAS) AF: 0.714 AC: 3434 AN: 4808

European-Finnish (FIN) AF: 0.573 AC: 6021 AN: 10512

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38825 AN: 67864

Other (OTH) AF: 0.580 AC: 1223 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		0.066
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: rs2229586; hg19: chr1-24200903; COSMIC: COSV65692721;