rs2023239

chr6-88150763-T-C

Variant summary

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

The NM_016083.6(CNR1):c.-63-5426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,188 control chromosomes in the GnomAD database, including 3,692 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 (3692 hom., cov: 32)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNR1	NM_016083.6	c.-63-5426A>G		intron_variant		ENST00000369501.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNR1	ENST00000369501.3	c.-63-5426A>G		intron_variant		1	NM_016083.6	P1
CNR1	ENST00000428600.3	c.-63-5426A>G		intron_variant		1		P1
CNR1	ENST00000369499.3	c.-63-5426A>G		intron_variant		5		P1
CNR1	ENST00000551417.2	c.-206-2957A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30857 AN: 152070 Hom.: 3683 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.203 AC: 30883 AN: 152188 Hom.: 3692 Cov.: 32 AF XY: 0.197 AC XY: 14683 AN XY: 74424

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.188

Alfa AF: 0.197 Hom.: 620

Bravo AF: 0.211

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.1
Dann	Benign	0.72

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: rs2023239; hg19: chr6-88860482;