dbSNP rs6454674: CNR1:c.-64+2592A>C (chr6-88163211-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016083.6(CNR1):c.-64+2592A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,106 control chromosomes in the GnomAD database, including 8,000 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 0.32 ( 8000 hom., cov: 33)

Consequence

CNR1
NM_016083.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

Publications

64 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:

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new If you want to explore the variant's impact on the transcript NM_016083.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 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.-64+2592A>C	intron	N/A	NP_057167.2
CNR1	NM_001160226.3		c.-207+2592A>C	intron	N/A	NP_001153698.1	P21554-1
CNR1	NM_001160258.3		c.-207+1046A>C	intron	N/A	NP_001153730.1	P21554-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNR1	ENST00000369501.3	TSL:1 MANE Select	c.-64+2592A>C	intron	N/A	ENSP00000358513.2	P21554-1
CNR1	ENST00000369499.3	TSL:5	c.-64+1046A>C	intron	N/A	ENSP00000358511.2	P21554-1
CNR1	ENST00000551417.2	TSL:5	c.-207+1046A>C	intron	N/A	ENSP00000446702.2	P21554-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49119

AN:

151988

Hom.:

7986

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.323

AC:

49165

AN:

152106

Hom.:

8000

Cov.:

AF XY:

0.326

AC XY:

24216

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.342

AC:

14214

AN:

41502

American (AMR)

AF:

0.318

AC:

4856

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

865

AN:

3468

East Asian (EAS)

AF:

0.280

AC:

1452

AN:

5186

South Asian (SAS)

AF:

0.297

AC:

1430

AN:

4822

European-Finnish (FIN)

AF:

0.366

AC:

3869

AN:

10576

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21321

AN:

67944

Other (OTH)

AF:

0.356

AC:

754

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1731

3462

5193

6924

8655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.315

Hom.:

19526

Bravo

AF:

0.322

Asia WGS

AF:

0.332

AC:

1153

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.5

(source)

DANN

Benign

0.44

PhyloP100

-1.3

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over