rs2501431

Variant names:

• chr1-23875153-G-A
• rs2501431
• NM_001841.3:c.465C>T

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.465C>T​(p.Gly155Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,120 control chromosomes in the GnomAD database, including 286,927 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 (30980 hom., cov: 31)
  • Exomes 𝑓: 0.59 (255947 hom.)
• Consequence: CNR2 NM_001841.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 46 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=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.057 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.465C>T	p.Gly155Gly	synonymous_variant	Exon 2 of 2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.465C>T	p.Gly155Gly	synonymous_variant	Exon 2 of 2		XP_011538931.1
CNR2	XM_017000261.3	c.465C>T	p.Gly155Gly	synonymous_variant	Exon 3 of 3		XP_016855750.1
CNR2	XM_047444833.1	c.465C>T	p.Gly155Gly	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.465C>T	p.Gly155Gly	synonymous_variant	Exon 2 of 2	1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96350 AN: 151892 Hom.: 30970 Cov.: 31

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.618

GnomAD2 exomes AF: 0.617 AC: 154609 AN: 250408 AF XY: 0.618

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.529

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.574

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.589 AC: 861136 AN: 1461110 Hom.: 255947 Cov.: 66 AF XY: 0.593 AC XY: 430815 AN XY: 726816

African (AFR) AF: 0.766 AC: 25625 AN: 33474

American (AMR) AF: 0.680 AC: 30384 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 14919 AN: 26020

East Asian (EAS) AF: 0.569 AC: 22584 AN: 39692

South Asian (SAS) AF: 0.719 AC: 61994 AN: 86184

European-Finnish (FIN) AF: 0.574 AC: 30619 AN: 53380

Middle Eastern (MID) AF: 0.709 AC: 4090 AN: 5766

European-Non Finnish (NFE) AF: 0.571 AC: 635087 AN: 1111540

Other (OTH) AF: 0.594 AC: 35834 AN: 60370

GnomAD4 genome AF: 0.634 AC: 96402 AN: 152010 Hom.: 30980 Cov.: 31 AF XY: 0.637 AC XY: 47346 AN XY: 74286

African (AFR) AF: 0.756 AC: 31345 AN: 41460

American (AMR) AF: 0.641 AC: 9790 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2014 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2705 AN: 5160

South Asian (SAS) AF: 0.713 AC: 3436 AN: 4820

European-Finnish (FIN) AF: 0.576 AC: 6077 AN: 10550

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

European-Non Finnish (NFE) AF: 0.574 AC: 39036 AN: 67960

Other (OTH) AF: 0.612 AC: 1296 AN: 2116

Alfa AF: 0.600 Hom.: 79117

Bravo AF: 0.644

Asia WGS AF: 0.631 AC: 2194 AN: 3478

EpiCase AF: 0.578

EpiControl AF: 0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.3
DANN	Benign	0.56
PhyloP100		-0.057
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: rs2501431; hg19: chr1-24201643; COSMIC: COSV65695038;