6-88148802-A-T

Variant names:

• chr6-88148802-A-T
• rs806375
• NM_016083.6:c.-63-3465T>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.-63-3465T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,010 control chromosomes in the GnomAD database, including 14,590 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 0.43 (14590 hom., cov: 32)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 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.-63-3465T>A		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-206-996T>A		intron	N/A	NP_001153698.1	P21554-1
	CNR1	NM_001160258.3		c.-206-996T>A		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.-63-3465T>A		intron	N/A	ENSP00000358513.2	P21554-1
	CNR1	ENST00000428600.3	TSL:1	c.-63-3465T>A		intron	N/A	ENSP00000412192.2	P21554-1
	CNR1	ENST00000918491.1		c.-1202T>A		5_prime_UTR	Exon 1 of 2	ENSP00000588550.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65706 AN: 151892 Hom.: 14578 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.433 AC: 65749 AN: 152010 Hom.: 14590 Cov.: 32 AF XY: 0.429 AC XY: 31886 AN XY: 74292

African (AFR) AF: 0.498 AC: 20639 AN: 41466

American (AMR) AF: 0.331 AC: 5048 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5162

South Asian (SAS) AF: 0.364 AC: 1752 AN: 4816

European-Finnish (FIN) AF: 0.448 AC: 4732 AN: 10554

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29655 AN: 67964

Other (OTH) AF: 0.453 AC: 955 AN: 2106

Alfa AF: 0.436 Hom.: 1799

Bravo AF: 0.426

Asia WGS AF: 0.316 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		0.055
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: rs806375; hg19: chr6-88858521;