1-23874958-C-T

Variant names:

• chr1-23874958-C-T
• rs3003336
• NM_001841.3:c.660G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001841.3(CNR2):​c.660G>A​(p.Val220Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,609,918 control chromosomes in the GnomAD database, including 286,209 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 (31018 hom., cov: 32)
  • Exomes 𝑓: 0.59 (255191 hom.)
• Consequence: CNR2 NM_001841.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 22 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.899 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR2	NM_001841.3	c.660G>A	p.Val220Val	synonymous_variant	Exon 2 of 2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.660G>A	p.Val220Val	synonymous_variant	Exon 2 of 2		XP_011538931.1
CNR2	XM_017000261.3	c.660G>A	p.Val220Val	synonymous_variant	Exon 3 of 3		XP_016855750.1
CNR2	XM_047444833.1	c.660G>A	p.Val220Val	synonymous_variant	Exon 2 of 2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.660G>A	p.Val220Val	synonymous_variant	Exon 2 of 2	1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96445 AN: 152010 Hom.: 31008 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.619

GnomAD2 exomes AF: 0.617 AC: 153065 AN: 248118 AF XY: 0.617

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.574

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.611

GnomAD4 exome AF: 0.589 AC: 858929 AN: 1457790 Hom.: 255191 Cov.: 56 AF XY: 0.593 AC XY: 429438 AN XY: 724764

African (AFR) AF: 0.765 AC: 25579 AN: 33418

American (AMR) AF: 0.680 AC: 30164 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 14789 AN: 25824

East Asian (EAS) AF: 0.569 AC: 22557 AN: 39644

South Asian (SAS) AF: 0.719 AC: 61701 AN: 85828

European-Finnish (FIN) AF: 0.574 AC: 30539 AN: 53248

Middle Eastern (MID) AF: 0.710 AC: 4081 AN: 5750

European-Non Finnish (NFE) AF: 0.571 AC: 633811 AN: 1109560

Other (OTH) AF: 0.594 AC: 35708 AN: 60164

GnomAD4 genome AF: 0.634 AC: 96497 AN: 152128 Hom.: 31018 Cov.: 32 AF XY: 0.638 AC XY: 47408 AN XY: 74356

African (AFR) AF: 0.756 AC: 31386 AN: 41520

American (AMR) AF: 0.641 AC: 9800 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2712 AN: 5162

South Asian (SAS) AF: 0.714 AC: 3444 AN: 4826

European-Finnish (FIN) AF: 0.576 AC: 6093 AN: 10570

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39056 AN: 67984

Other (OTH) AF: 0.613 AC: 1293 AN: 2110

Alfa AF: 0.602 Hom.: 13425

Bravo AF: 0.644

Asia WGS AF: 0.631 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.54
PhyloP100		-0.90
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: rs3003336; hg19: chr1-24201448; COSMIC: COSV65692451;