6-88156102-A-T

Variant summary

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

The NM_016083.6(CNR1):c.-64+9701T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 152,256 control chromosomes in the GnomAD database, including 89 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 0.024 (89 hom., cov: 32)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNR1	NM_016083.6	c.-64+9701T>A		intron_variant		ENST00000369501.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNR1	ENST00000369501.3	c.-64+9701T>A		intron_variant		1	NM_016083.6	P1
CNR1	ENST00000428600.3	c.-64+6855T>A		intron_variant		1		P1
CNR1	ENST00000369499.3	c.-64+8155T>A		intron_variant		5		P1
CNR1	ENST00000551417.2	c.-207+8155T>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3709 AN: 152138 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00683

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0244 AC: 3718 AN: 152256 Hom.: 89 Cov.: 32 AF XY: 0.0278 AC XY: 2067 AN XY: 74444

Gnomad4 AFR AF: 0.00679

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.0653

Gnomad4 SAS AF: 0.0426

Gnomad4 FIN AF: 0.0436

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0189 Hom.: 5

Bravo AF: 0.0278

Asia WGS AF: 0.0990 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.93
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: rs2057276; hg19: chr6-88865821;