1-23895344-T-G

Variant names:

• chr1-23895344-T-G
• rs9424398
• NM_001841.3:c.-46+17902A>C

Variant summary

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

The NM_001841.3(CNR2):​c.-46+17902A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,140 control chromosomes in the GnomAD database, including 50,946 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 (50946 hom., cov: 33)
• Consequence: CNR2 NM_001841.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 14 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=-0.89).
• 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 rank	MANE	Protein	UniProt
CNR2	NM_001841.3	c.-46+17902A>C		intron_variant	Intron 1 of 1	ENST00000374472.5	NP_001832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.-46+17902A>C		intron_variant	Intron 1 of 1	1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124294 AN: 152022 Hom.: 50913 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.818 AC: 124376 AN: 152140 Hom.: 50946 Cov.: 33 AF XY: 0.820 AC XY: 61029 AN XY: 74386

African (AFR) AF: 0.826 AC: 34292 AN: 41492

American (AMR) AF: 0.836 AC: 12768 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2648 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3366 AN: 5182

South Asian (SAS) AF: 0.820 AC: 3955 AN: 4826

European-Finnish (FIN) AF: 0.880 AC: 9326 AN: 10594

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55293 AN: 67988

Other (OTH) AF: 0.809 AC: 1708 AN: 2112

Alfa AF: 0.812 Hom.: 76689

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	-0.89
CADD	Benign	3.2
DANN	Benign	0.61
PhyloP100		-0.13
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: rs9424398; hg19: chr1-24221834; COSMIC: COSV65692552;