rs806376

Variant names:

• chr6-88148929-T-C
• rs806376
• NM_016083.6:c.-63-3592A>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.-63-3592A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,052 control chromosomes in the GnomAD database, including 20,695 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 0.51 (20695 hom., cov: 32)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 14 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-3592A>G		intron_variant	Intron 1 of 1	ENST00000369501.3	NP_057167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR1	ENST00000369501.3	c.-63-3592A>G		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77632 AN: 151934 Hom.: 20672 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.511 AC: 77693 AN: 152052 Hom.: 20695 Cov.: 32 AF XY: 0.505 AC XY: 37536 AN XY: 74320

African (AFR) AF: 0.646 AC: 26794 AN: 41468

American (AMR) AF: 0.397 AC: 6066 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1247 AN: 5172

South Asian (SAS) AF: 0.422 AC: 2035 AN: 4820

European-Finnish (FIN) AF: 0.481 AC: 5072 AN: 10554

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33405 AN: 67970

Other (OTH) AF: 0.525 AC: 1108 AN: 2110

Alfa AF: 0.493 Hom.: 74834

Bravo AF: 0.510

Asia WGS AF: 0.353 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.67
PhyloP100		-0.34
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: rs806376; hg19: chr6-88858648;