1-23874431-T-C

Variant names:

• chr1-23874431-T-C
• rs2229585
• NM_001841.3:c.*104A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001841.3(CNR2):​c.*104A>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 0.586 in 1,295,458 control chromosomes in the GnomAD database, including 224,855 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 (30836 hom., cov: 32)
  • Exomes 𝑓: 0.58 (194019 hom.)
• Consequence: CNR2 NM_001841.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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=-0.89).
• 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 rank	MANE	Protein	UniProt
CNR2	NM_001841.3	c.*104A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.*104A>G		3_prime_UTR_variant	Exon 2 of 2		XP_011538931.1
CNR2	XM_017000261.3	c.*104A>G		3_prime_UTR_variant	Exon 3 of 3		XP_016855750.1
CNR2	XM_047444833.1	c.*104A>G		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	c.*104A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96074 AN: 151614 Hom.: 30826 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.702

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.579 AC: 662532 AN: 1143726 Hom.: 194019 Cov.: 16 AF XY: 0.584 AC XY: 333459 AN XY: 571230

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.569

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.717

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.586

GnomAD4 genome AF: 0.634 AC: 96126 AN: 151732 Hom.: 30836 Cov.: 32 AF XY: 0.636 AC XY: 47178 AN XY: 74134

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.612

Alfa AF: 0.602 Hom.: 8628

Bravo AF: 0.644

Asia WGS AF: 0.630 AC: 2190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.70

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: rs2229585; hg19: chr1-24200921;