Genetic Variant CNR1:c.*2612C>A (chr6-88141244-G-T) – 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.*2612C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,766 control chromosomes in the GnomAD database, including 850 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 0.088 ( 843 hom., cov: 32)

Exomes 𝑓: 0.17 ( 7 hom. )

Consequence

CNR1
NM_016083.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.244

Publications

4 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6 link	c.*2612C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000369501.3	NP_057167.2	P21554-1S5TLS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR1	ENST00000369501.3 link	c.*2612C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_016083.6	ENSP00000358513.2		P21554-1

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13441

AN:

152086

Hom.:

844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.0672

Gnomad ASJ

AF:

0.0849

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0394

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.0998

GnomAD4 exome

AF:

0.165

AC:

AN:

562

Hom.:

Cov.:

AF XY:

0.168

AC XY:

AN XY:

334

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.112

AC:

AN:

134

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.185

AC:

AN:

422

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

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:

0.0883

AC:

13436

AN:

152204

Hom.:

843

Cov.:

AF XY:

0.0880

AC XY:

6548

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0206

AC:

855

AN:

41544

American (AMR)

AF:

0.0671

AC:

1026

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0849

AC:

294

AN:

3464

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.0394

AC:

190

AN:

4822

European-Finnish (FIN)

AF:

0.170

AC:

1797

AN:

10572

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8939

AN:

68000

Other (OTH)

AF:

0.0988

AC:

208

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

609

1217

1826

2434

3043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0746

Hom.:

151

Bravo

AF:

0.0797

Asia WGS

AF:

0.0170

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.68

PhyloP100

-0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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