rs806374

chr6-88147601-T-Cchr6-88147601-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016083.6(CNR1):c.-63-2264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,040 control chromosomes in the GnomAD database, including 10,715 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 0.37 (10714 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNR1	NM_016083.6	c.-63-2264A>G		intron_variant		ENST00000369501.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNR1	ENST00000369501.3	c.-63-2264A>G		intron_variant		1	NM_016083.6	P1
CNR1	ENST00000428600.3	c.-63-2264A>G		intron_variant		1		P1
CNR1	ENST00000369499.3	c.-63-2264A>G		intron_variant		5		P1
CNR1	ENST00000551417.2	c.-64+63A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56439 AN: 151892 Hom.: 10685 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.300 AC: 9 AN: 30 Hom.: 1 AF XY: 0.227 AC XY: 5 AN XY: 22

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.273

GnomAD4 genome AF: 0.372 AC: 56523 AN: 152010 Hom.: 10714 Cov.: 32 AF XY: 0.372 AC XY: 27640 AN XY: 74310

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.379

Alfa AF: 0.351 Hom.: 16487

Bravo AF: 0.381

Asia WGS AF: 0.430 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.10
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs806374; hg19: chr6-88857320;