1-23875430-T-G

Variant names:

• chr1-23875430-T-G
• rs2501432
• NM_001841.3:c.188A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001841.3(CNR2):​c.188A>C​(p.Gln63Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNR2 NM_001841.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 63 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1710409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR2	NM_001841.3	c.188A>C	p.Gln63Pro	missense_variant	Exon 2 of 2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.188A>C	p.Gln63Pro	missense_variant	Exon 2 of 2		XP_011538931.1
CNR2	XM_017000261.3	c.188A>C	p.Gln63Pro	missense_variant	Exon 3 of 3		XP_016855750.1
CNR2	XM_047444833.1	c.188A>C	p.Gln63Pro	missense_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.188A>C	p.Gln63Pro	missense_variant	Exon 2 of 2	1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 48283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.63	N
PhyloP100		1.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.16
Sift	Benign	0.064	T
Sift4G	Benign	0.28	T
Vest4		0.20
ClinPred		0.081	T
GERP RS		5.1
Varity_R		0.50
gMVP		0.62
Mutation Taster		=86/14	polymorphism

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: rs2501432; hg19: chr1-24201920;