rs12720071

Positions:

• chr6-88141462-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.*2394A>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 0.105 in 152,484 control chromosomes in the GnomAD database, including 991 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 0.10 (988 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: CNR1 NM_016083.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR1	NM_016083.6	c.*2394A>G		3_prime_UTR_variant	2/2	ENST00000369501.3	NP_057167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR1	ENST00000369501.3	c.*2394A>G		3_prime_UTR_variant	2/2	1	NM_016083.6	ENSP00000358513	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15900 AN: 152154 Hom.: 983 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0609

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.118 AC: 25 AN: 212 Hom.: 3 Cov.: 0 AF XY: 0.152 AC XY: 17 AN XY: 112

Gnomad4 EAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.105 AC: 15935 AN: 152272 Hom.: 988 Cov.: 32 AF XY: 0.101 AC XY: 7553 AN XY: 74466

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0757

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.110

Alfa AF: 0.101 Hom.: 271

Bravo AF: 0.108

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.6
DANN	Benign	0.74

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: rs12720071; hg19: chr6-88851181;