rs9450898

Variant names:

• chr6-88154344-C-T
• rs9450898
• NM_016083.6:c.-63-9007G>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.-63-9007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,118 control chromosomes in the GnomAD database, including 3,535 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 0.20 (3535 hom., cov: 33)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 12 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-9007G>A		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.-63-9007G>A		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30392 AN: 152000 Hom.: 3527 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.200 AC: 30415 AN: 152118 Hom.: 3535 Cov.: 33 AF XY: 0.194 AC XY: 14460 AN XY: 74362

African (AFR) AF: 0.320 AC: 13263 AN: 41486

American (AMR) AF: 0.142 AC: 2166 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3468

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5178

South Asian (SAS) AF: 0.149 AC: 715 AN: 4814

European-Finnish (FIN) AF: 0.130 AC: 1370 AN: 10574

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11605 AN: 67984

Other (OTH) AF: 0.182 AC: 385 AN: 2116

Alfa AF: 0.201 Hom.: 534

Bravo AF: 0.207

Asia WGS AF: 0.104 AC: 365 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.066
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: rs9450898; hg19: chr6-88864063;