Genetic Variant CNR1:c.*1824C>T (chr6-88142032-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016083.6(CNR1):c.*1824C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,100 control chromosomes in the GnomAD database, including 7,392 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 0.30 ( 7388 hom., cov: 32)

Exomes 𝑓: 0.29 ( 4 hom. )

Consequence

CNR1
NM_016083.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

Publications

29 publications found

Variant links:

Genes affected

CNR1 (HGNC:2159): (cannabinoid receptor 1) This gene encodes one of two cannabinoid receptors. The cannabinoids, principally delta-9-tetrahydrocannabinol and synthetic analogs, are psychoactive ingredients of marijuana. The cannabinoid receptors are members of the guanine-nucleotide-binding protein (G-protein) coupled receptor family, which inhibit adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. The two receptors have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. Multiple transcript variants encoding two different protein isoforms have been described for this gene. [provided by RefSeq, May 2009]

CNR1 links:

ENSG00000298549 (HGNC:):

ENSG00000298549 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016083.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNR1	NM_016083.6	MANE Select	c.*1824C>T	3_prime_UTR	Exon 2 of 2	NP_057167.2
CNR1	NM_001160226.3		c.*1824C>T	3_prime_UTR	Exon 3 of 3	NP_001153698.1	P21554-1
CNR1	NM_001160258.3		c.*1824C>T	3_prime_UTR	Exon 4 of 4	NP_001153730.1	P21554-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNR1	ENST00000369501.3	TSL:1 MANE Select	c.*1824C>T	3_prime_UTR	Exon 2 of 2	ENSP00000358513.2	P21554-1
CNR1	ENST00000428600.3	TSL:1	c.*1824C>T	3_prime_UTR	Exon 2 of 2	ENSP00000412192.2	P21554-1
CNR1	ENST00000468898.2	TSL:1	c.*1824C>T	3_prime_UTR	Exon 2 of 2	ENSP00000420188.1	P21554-3

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45533

AN:

151826

Hom.:

7395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.0775

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.247

GnomAD4 exome

AF:

0.295

AC:

AN:

156

Hom.:

Cov.:

AF XY:

0.291

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.287

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.300

AC:

45543

AN:

151944

Hom.:

7388

Cov.:

AF XY:

0.295

AC XY:

21895

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.414

AC:

17147

AN:

41422

American (AMR)

AF:

0.219

AC:

3349

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

685

AN:

3468

East Asian (EAS)

AF:

0.0775

AC:

401

AN:

5176

South Asian (SAS)

AF:

0.175

AC:

843

AN:

4812

European-Finnish (FIN)

AF:

0.311

AC:

3270

AN:

10530

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19058

AN:

67956

Other (OTH)

AF:

0.242

AC:

511

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1610

3220

4829

6439

8049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.278

Hom.:

8083

Bravo

AF:

0.297

Asia WGS

AF:

0.130

AC:

452

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.1

(source)

DANN

Benign

0.56

PhyloP100

2.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over