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GeneBe

6-88144363-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_016083.6(CNR1):c.912C>T(p.His304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,884 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 17 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 28 hom. )

Consequence

CNR1
NM_016083.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.815
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-88144363-G-A is Benign according to our data. Variant chr6-88144363-G-A is described in ClinVar as [Benign]. Clinvar id is 771863.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.815 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00694 (1057/152264) while in subpopulation AFR AF= 0.02 (832/41538). AF 95% confidence interval is 0.0189. There are 17 homozygotes in gnomad4. There are 509 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1060 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNR1NM_016083.6 linkuse as main transcriptc.912C>T p.His304= synonymous_variant 2/2 ENST00000369501.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNR1ENST00000369501.3 linkuse as main transcriptc.912C>T p.His304= synonymous_variant 2/21 NM_016083.6 P1P21554-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00697
AC:
1060
AN:
152146
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0202
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00498
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00146
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00311
AC:
779
AN:
250288
Hom.:
12
AF XY:
0.00281
AC XY:
381
AN XY:
135488
show subpopulations
Gnomad AFR exome
AF:
0.0212
Gnomad AMR exome
AF:
0.00318
Gnomad ASJ exome
AF:
0.00757
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00137
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00165
Gnomad OTH exome
AF:
0.00327
GnomAD4 exome
AF:
0.00173
AC:
2522
AN:
1461620
Hom.:
28
Cov.:
33
AF XY:
0.00166
AC XY:
1204
AN XY:
727092
show subpopulations
Gnomad4 AFR exome
AF:
0.0215
Gnomad4 AMR exome
AF:
0.00389
Gnomad4 ASJ exome
AF:
0.00735
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00101
Gnomad4 FIN exome
AF:
0.000113
Gnomad4 NFE exome
AF:
0.000859
Gnomad4 OTH exome
AF:
0.00421
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00694
AC:
1057
AN:
152264
Hom.:
17
Cov.:
32
AF XY:
0.00684
AC XY:
509
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0200
Gnomad4 AMR
AF:
0.00497
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00146
Gnomad4 OTH
AF:
0.00805
Alfa
AF:
0.00494
Hom.:
1
Bravo
AF:
0.00864
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.00185
EpiControl
AF:
0.00261

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 06, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
Cadd
Benign
0.25
Dann
Benign
0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144233963; hg19: chr6-88854082; API