1-23893573-A-G

Position:

• chr1-23893573-A-G

Variant summary

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

The NM_001841.3(CNR2):​c.-45-17911T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,172 control chromosomes in the GnomAD database, including 50,737 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 0.82 (50737 hom., cov: 32)
• Consequence: CNR2 NM_001841.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR2	NM_001841.3	c.-45-17911T>C		intron_variant		ENST00000374472.5	NP_001832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.-45-17911T>C		intron_variant		1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124056 AN: 152054 Hom.: 50708 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.813

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.816 AC: 124135 AN: 152172 Hom.: 50737 Cov.: 32 AF XY: 0.819 AC XY: 60915 AN XY: 74394

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.807

Alfa AF: 0.799 Hom.: 3566

Bravo AF: 0.813

Asia WGS AF: 0.751 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.47

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: rs2501401; hg19: chr1-24220063; COSMIC: COSV65692524;