rs806381

Variant names:

• chr6-88156182-A-G
• rs806381
• NM_016083.6:c.-64+9621T>C

Variant summary

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

The NM_016083.6(CNR1):​c.-64+9621T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,056 control chromosomes in the GnomAD database, including 7,889 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 (7889 hom., cov: 32)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• 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 (AMR) allele frequency at 95% confidence interval = 0.321 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.-64+9621T>C		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-206-8376T>C		intron	N/A	NP_001153698.1	P21554-1
	CNR1	NM_001160258.3		c.-207+8075T>C		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.-64+9621T>C		intron	N/A	ENSP00000358513.2	P21554-1
	CNR1	ENST00000428600.3	TSL:1	c.-64+6775T>C		intron	N/A	ENSP00000412192.2	P21554-1
	CNR1	ENST00000369499.3	TSL:5	c.-64+8075T>C		intron	N/A	ENSP00000358511.2	P21554-1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48794 AN: 151938 Hom.: 7877 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.321 AC: 48839 AN: 152056 Hom.: 7889 Cov.: 32 AF XY: 0.324 AC XY: 24114 AN XY: 74320

African (AFR) AF: 0.307 AC: 12742 AN: 41466

American (AMR) AF: 0.327 AC: 4990 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1502 AN: 5182

South Asian (SAS) AF: 0.302 AC: 1457 AN: 4818

European-Finnish (FIN) AF: 0.379 AC: 4006 AN: 10566

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22085 AN: 67976

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.322 Hom.: 21162

Bravo AF: 0.319

Asia WGS AF: 0.337 AC: 1173 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	0.64
DANN	Benign	0.25
PhyloP100		-0.93
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: rs806381; hg19: chr6-88865901;