1-23875429-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001841.3(CNR2):​c.189A>C​(p.Gln63His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q63R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CNR2
NM_001841.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10336271).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNR2NM_001841.3 linkc.189A>C p.Gln63His missense_variant Exon 2 of 2 ENST00000374472.5 NP_001832.1 P34972A0A024RAH7
CNR2XM_011540629.4 linkc.189A>C p.Gln63His missense_variant Exon 2 of 2 XP_011538931.1 P34972A0A024RAH7
CNR2XM_017000261.3 linkc.189A>C p.Gln63His missense_variant Exon 3 of 3 XP_016855750.1 P34972A0A024RAH7
CNR2XM_047444833.1 linkc.189A>C p.Gln63His missense_variant Exon 2 of 2 XP_047300789.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNR2ENST00000374472.5 linkc.189A>C p.Gln63His missense_variant Exon 2 of 2 1 NM_001841.3 ENSP00000363596.4 P34972

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461770
Hom.:
0
Cov.:
68
AF XY:
0.00
AC XY:
0
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
12
DANN
Benign
0.91
DEOGEN2
Benign
0.091
T
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.98
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.41
N
REVEL
Benign
0.062
Sift
Benign
0.18
T
Sift4G
Benign
0.28
T
Polyphen
0.0
B
Vest4
0.025
MutPred
0.29
Loss of sheet (P = 0.0817);
MVP
0.67
ClinPred
0.062
T
GERP RS
3.0
Varity_R
0.20
gMVP
0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24201919; API