Genetic Variant CNR2:c.*104A>G (chr1-23874431-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001841.3(CNR2):c.*104A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,295,458 control chromosomes in the GnomAD database, including 224,855 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 ( 30836 hom., cov: 32)

Exomes 𝑓: 0.58 ( 194019 hom. )

Consequence

CNR2
NM_001841.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.602

Publications

10 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]

CNR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CNR2	NM_001841.3 link	c.*104A>G	3_prime_UTR_variant	Exon 2 of 2	ENST00000374472.5	NP_001832.1	P34972A0A024RAH7
CNR2	XM_011540629.4 link	c.*104A>G	3_prime_UTR_variant	Exon 2 of 2		XP_011538931.1	P34972A0A024RAH7
CNR2	XM_017000261.3 link	c.*104A>G	3_prime_UTR_variant	Exon 3 of 3		XP_016855750.1	P34972A0A024RAH7
CNR2	XM_047444833.1 link	c.*104A>G	3_prime_UTR_variant	Exon 2 of 2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5 link	c.*104A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001841.3	ENSP00000363596.4		P34972

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96074

AN:

151614

Hom.:

30826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.640

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.714

Gnomad FIN

AF:

0.574

Gnomad MID

AF:

0.702

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.618

GnomAD4 exome

AF:

0.579

AC:

662532

AN:

1143726

Hom.:

194019

Cov.:

AF XY:

0.584

AC XY:

333459

AN XY:

571230

show subpopulations

African (AFR)

AF:

0.758

AC:

19212

AN:

25356

American (AMR)

AF:

0.677

AC:

20493

AN:

30284

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

10807

AN:

18988

East Asian (EAS)

AF:

0.570

AC:

21623

AN:

37952

South Asian (SAS)

AF:

0.717

AC:

47305

AN:

65994

European-Finnish (FIN)

AF:

0.565

AC:

20514

AN:

36286

Middle Eastern (MID)

AF:

0.703

AC:

3068

AN:

4364

European-Non Finnish (NFE)

AF:

0.561

AC:

490703

AN:

875314

Other (OTH)

AF:

0.586

AC:

28807

AN:

49188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12577

25153

37730

50306

62883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13122

26244

39366

52488

65610

<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:

96126

AN:

151732

Hom.:

30836

Cov.:

AF XY:

0.636

AC XY:

47178

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.755

AC:

31291

AN:

41428

American (AMR)

AF:

0.641

AC:

9768

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

2007

AN:

3462

East Asian (EAS)

AF:

0.523

AC:

2686

AN:

5138

South Asian (SAS)

AF:

0.714

AC:

3435

AN:

4812

European-Finnish (FIN)

AF:

0.574

AC:

6025

AN:

10502

Middle Eastern (MID)

AF:

0.693

AC:

201

AN:

290

European-Non Finnish (NFE)

AF:

0.574

AC:

38939

AN:

67848

Other (OTH)

AF:

0.612

AC:

1287

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1832

3664

5495

7327

9159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.604

Hom.:

10985

Bravo

AF:

0.644

Asia WGS

AF:

0.630

AC:

2190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.70

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over