6-88146644-T-G

Position:

• chr6-88146644-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.-63-1307A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,254 control chromosomes in the GnomAD database, including 3,354 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 0.19 (3354 hom., cov: 33)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-1307A>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.-63-1307A>C		intron_variant		1	NM_016083.6	ENSP00000358513	P1
CNR1	ENST00000428600.3	c.-63-1307A>C		intron_variant		1		ENSP00000412192	P1
CNR1	ENST00000369499.3	c.-63-1307A>C		intron_variant		5		ENSP00000358511	P1
CNR1	ENST00000551417.2	c.-64+1020A>C		intron_variant		5		ENSP00000446702	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28685 AN: 152136 Hom.: 3339 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.189 AC: 28747 AN: 152254 Hom.: 3354 Cov.: 33 AF XY: 0.194 AC XY: 14424 AN XY: 74448

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.0850

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.213

Alfa AF: 0.149 Hom.: 255

Bravo AF: 0.207

Asia WGS AF: 0.361 AC: 1256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.91
DANN	Benign	0.73

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: rs806371; hg19: chr6-88856363;