6-88140381-T-C

Variant names:

• chr6-88140381-T-C
• rs806368
• NM_016083.6:c.*3475A>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.*3475A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,746 control chromosomes in the GnomAD database, including 3,686 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 (3671 hom., cov: 33)
  • Exomes 𝑓: 0.21 (15 hom.)
• Consequence: CNR1 NM_016083.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 126 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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 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.*3475A>G		3_prime_UTR	Exon 2 of 2	NP_057167.2
	CNR1	NM_001160226.3		c.*3475A>G		3_prime_UTR	Exon 3 of 3	NP_001153698.1
	CNR1	NM_001160258.3		c.*3475A>G		3_prime_UTR	Exon 4 of 4	NP_001153730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.*3475A>G		3_prime_UTR	Exon 2 of 2	ENSP00000358513.2
	CNR1	ENST00000428600.3	TSL:1	c.*3475A>G		3_prime_UTR	Exon 2 of 2	ENSP00000412192.2
	CNR1	ENST00000468898.2	TSL:1	c.*3475A>G		3_prime_UTR	Exon 2 of 2	ENSP00000420188.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30378 AN: 152060 Hom.: 3665 Cov.: 33

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.207 AC: 117 AN: 566 Hom.: 15 Cov.: 0 AF XY: 0.240 AC XY: 80 AN XY: 334

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.254 AC: 34 AN: 134

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.190 AC: 81 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.200 AC: 30410 AN: 152180 Hom.: 3671 Cov.: 33 AF XY: 0.204 AC XY: 15207 AN XY: 74398

African (AFR) AF: 0.0967 AC: 4017 AN: 41534

American (AMR) AF: 0.317 AC: 4842 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3466

East Asian (EAS) AF: 0.500 AC: 2587 AN: 5174

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1652 AN: 10584

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14134 AN: 68000

Other (OTH) AF: 0.237 AC: 502 AN: 2114

Alfa AF: 0.214 Hom.: 11699

Bravo AF: 0.208

Asia WGS AF: 0.375 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.67
PhyloP100		0.062
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: rs806368; hg19: chr6-88850100;