rs35761398

Variant names:

• chr1-23875429-TT-CC
• rs35761398
• NM_001841.3:c.188_189delAAinsGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001841.3(CNR2):​c.188_189delAAinsGG​(p.Gln63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.617 in 173,720 alleles, including 54,494 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: GnomAD MNV: 𝑓 0.62 Genomes: not found (cov: 33)
• Consequence: CNR2 NM_001841.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 137 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 -8 ACMG points.

• BA1: GnomAdMnv highest population allele frequency = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR2	NM_001841.3	c.188_189delAAinsGG	p.Gln63Arg	missense_variant		ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.188_189delAAinsGG	p.Gln63Arg	missense_variant			XP_011538931.1
CNR2	XM_017000261.3	c.188_189delAAinsGG	p.Gln63Arg	missense_variant			XP_016855750.1
CNR2	XM_047444833.1	c.188_189delAAinsGG	p.Gln63Arg	missense_variant			XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.188_189delAAinsGG	p.Gln63Arg	missense_variant		1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

GnomAD MNV AF: 0.617 AC: 173720 Hom.: 54494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35761398; hg19: chr1-24201919; COSMIC: COSV108224609;