NM_016083.6:c.-63-4495G>A

Variant names:

• chr6-88149832-C-T
• rs806378
• NM_016083.6:c.-63-4495G>A

Variant summary

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

The NM_016083.6(CNR1):​c.-63-4495G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,088 control chromosomes in the GnomAD database, including 3,971 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 0.21 (3971 hom., cov: 32)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 49 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	NM_016083.6	MANE Select	c.-63-4495G>A		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-206-2026G>A		intron	N/A	NP_001153698.1
	CNR1	NM_001160258.3		c.-206-2026G>A		intron	N/A	NP_001153730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.-63-4495G>A		intron	N/A	ENSP00000358513.2
	CNR1	ENST00000428600.3	TSL:1	c.-63-4495G>A		intron	N/A	ENSP00000412192.2
	CNR1	ENST00000369499.3	TSL:5	c.-63-4495G>A		intron	N/A	ENSP00000358511.2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31866 AN: 151970 Hom.: 3972 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.210 AC: 31867 AN: 152088 Hom.: 3971 Cov.: 32 AF XY: 0.212 AC XY: 15764 AN XY: 74346

African (AFR) AF: 0.0841 AC: 3491 AN: 41504

American (AMR) AF: 0.189 AC: 2886 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3472

East Asian (EAS) AF: 0.164 AC: 851 AN: 5190

South Asian (SAS) AF: 0.213 AC: 1023 AN: 4812

European-Finnish (FIN) AF: 0.313 AC: 3309 AN: 10556

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18882 AN: 67952

Other (OTH) AF: 0.241 AC: 508 AN: 2110

Alfa AF: 0.247 Hom.: 12720

Bravo AF: 0.195

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.48
DANN	Benign	0.68
PhyloP100		-0.93
Mutation Taster		=300/0	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: rs806378; hg19: chr6-88859551;