rs6454674

Positions:

• chr6-88163211-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.-64+2592A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,106 control chromosomes in the GnomAD database, including 8,000 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 0.32 (8000 hom., cov: 33)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-64+2592A>C		intron_variant		ENST00000369501.3	NP_057167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR1	ENST00000369501.3	c.-64+2592A>C		intron_variant		1	NM_016083.6	ENSP00000358513	P1
CNR1	ENST00000369499.3	c.-64+1046A>C		intron_variant		5		ENSP00000358511	P1
CNR1	ENST00000551417.2	c.-207+1046A>C		intron_variant		5		ENSP00000446702	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49119 AN: 151988 Hom.: 7986 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.323 AC: 49165 AN: 152106 Hom.: 8000 Cov.: 33 AF XY: 0.326 AC XY: 24216 AN XY: 74346

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.356

Alfa AF: 0.314 Hom.: 7005

Bravo AF: 0.322

Asia WGS AF: 0.332 AC: 1153 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs6454674; hg19: chr6-88872930;