6-88146459-T-C

Variant names:

• chr6-88146459-T-C
• rs806369
• NM_016083.6:c.-63-1122A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016083.6(CNR1):​c.-63-1122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,050 control chromosomes in the GnomAD database, including 42,401 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 0.74 (42401 hom., cov: 31)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 27 publications found

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]

ENSG00000298549 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	NM_016083.6	MANE Select	c.-63-1122A>G		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-63-1122A>G		intron	N/A	NP_001153698.1	P21554-1
	CNR1	NM_001160258.3		c.-63-1122A>G		intron	N/A	NP_001153730.1	P21554-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.-63-1122A>G		intron	N/A	ENSP00000358513.2	P21554-1
	CNR1	ENST00000428600.3	TSL:1	c.-63-1122A>G		intron	N/A	ENSP00000412192.2	P21554-1
	CNR1	ENST00000369499.3	TSL:5	c.-63-1122A>G		intron	N/A	ENSP00000358511.2	P21554-1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112632 AN: 151932 Hom.: 42352 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.741 AC: 112738 AN: 152050 Hom.: 42401 Cov.: 31 AF XY: 0.738 AC XY: 54872 AN XY: 74332

African (AFR) AF: 0.869 AC: 36044 AN: 41496

American (AMR) AF: 0.691 AC: 10568 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3472

East Asian (EAS) AF: 0.582 AC: 3006 AN: 5162

South Asian (SAS) AF: 0.688 AC: 3311 AN: 4810

European-Finnish (FIN) AF: 0.695 AC: 7338 AN: 10564

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.706 AC: 47957 AN: 67946

Other (OTH) AF: 0.723 AC: 1529 AN: 2114

Alfa AF: 0.707 Hom.: 48044

Bravo AF: 0.745

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.39
DANN	Benign	0.37
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs806369; hg19: chr6-88856178;