chr6-88140381-T-C

Position:

• chr6-88140381-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.*3475A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,746 control chromosomes in the GnomAD database, including 3,686 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 (3671 hom., cov: 33)
  • Exomes 𝑓: 0.21 (15 hom.)
• Consequence: CNR1 NM_016083.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNR1	NM_016083.6	c.*3475A>G		3_prime_UTR_variant	2/2	ENST00000369501.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNR1	ENST00000369501.3	c.*3475A>G		3_prime_UTR_variant	2/2	1	NM_016083.6	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30378 AN: 152060 Hom.: 3665 Cov.: 33

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.207 AC: 117 AN: 566 Hom.: 15 Cov.: 0 AF XY: 0.240 AC XY: 80 AN XY: 334

Gnomad4 EAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.200 AC: 30410 AN: 152180 Hom.: 3671 Cov.: 33 AF XY: 0.204 AC XY: 15207 AN XY: 74398

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.237

Alfa AF: 0.217 Hom.: 5070

Bravo AF: 0.208

Asia WGS AF: 0.375 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.67

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: rs806368; hg19: chr6-88850100;