NM_001841.3:c.846T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001841.3(CNR2):​c.846T>C​(p.Ala282Ala) 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 1,613,860 control chromosomes in the GnomAD database, including 287,075 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 ( 31020 hom., cov: 32)
Exomes 𝑓: 0.59 ( 256055 hom. )

Consequence

CNR2
NM_001841.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.431

Publications

23 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP7
Synonymous conserved (PhyloP=0.431 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
CNR2NM_001841.3 linkc.846T>C p.Ala282Ala synonymous_variant Exon 2 of 2 ENST00000374472.5 NP_001832.1 P34972A0A024RAH7
CNR2XM_011540629.4 linkc.846T>C p.Ala282Ala synonymous_variant Exon 2 of 2 XP_011538931.1 P34972A0A024RAH7
CNR2XM_017000261.3 linkc.846T>C p.Ala282Ala synonymous_variant Exon 3 of 3 XP_016855750.1 P34972A0A024RAH7
CNR2XM_047444833.1 linkc.846T>C p.Ala282Ala synonymous_variant Exon 2 of 2 XP_047300789.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNR2ENST00000374472.5 linkc.846T>C p.Ala282Ala synonymous_variant Exon 2 of 2 1 NM_001841.3 ENSP00000363596.4 P34972

Frequencies

GnomAD3 genomes
AF:
0.635
AC:
96436
AN:
151958
Hom.:
31010
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.757
Gnomad AMI
AF:
0.550
Gnomad AMR
AF:
0.641
Gnomad ASJ
AF:
0.581
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:
155135
AN:
251322
AF XY:
0.618
show subpopulations
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:
0.583
Gnomad NFE exome
AF:
0.574
Gnomad OTH exome
AF:
0.611
GnomAD4 exome
AF:
0.589
AC:
861510
AN:
1461784
Hom.:
256055
Cov.:
61
AF XY:
0.593
AC XY:
431033
AN XY:
727206
show subpopulations
African (AFR)
AF:
0.766
AC:
25628
AN:
33478
American (AMR)
AF:
0.680
AC:
30395
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.573
AC:
14982
AN:
26134
East Asian (EAS)
AF:
0.569
AC:
22581
AN:
39686
South Asian (SAS)
AF:
0.719
AC:
62042
AN:
86256
European-Finnish (FIN)
AF:
0.574
AC:
30635
AN:
53408
Middle Eastern (MID)
AF:
0.710
AC:
4093
AN:
5768
European-Non Finnish (NFE)
AF:
0.571
AC:
635312
AN:
1111942
Other (OTH)
AF:
0.593
AC:
35842
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
20237
40473
60710
80946
101183
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
17784
35568
53352
71136
88920
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.634
AC:
96488
AN:
152076
Hom.:
31020
Cov.:
32
AF XY:
0.638
AC XY:
47402
AN XY:
74352
show subpopulations
African (AFR)
AF:
0.756
AC:
31401
AN:
41520
American (AMR)
AF:
0.641
AC:
9802
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.581
AC:
2014
AN:
3468
East Asian (EAS)
AF:
0.525
AC:
2703
AN:
5152
South Asian (SAS)
AF:
0.714
AC:
3444
AN:
4826
European-Finnish (FIN)
AF:
0.576
AC:
6099
AN:
10580
Middle Eastern (MID)
AF:
0.694
AC:
204
AN:
294
European-Non Finnish (NFE)
AF:
0.574
AC:
39028
AN:
67934
Other (OTH)
AF:
0.613
AC:
1294
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
1844
3688
5532
7376
9220
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
792
1584
2376
3168
3960
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.598
Hom.:
43487
Bravo
AF:
0.644
Asia WGS
AF:
0.632
AC:
2197
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
-0.67
CADD
Benign
8.6
DANN
Benign
0.69
PhyloP100
0.43
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs2502993; hg19: chr1-24201262; COSMIC: COSV65692447; API