rs12720071

Variant names:

• chr6-88141462-T-C
• rs12720071
• NM_016083.6:c.*2394A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 75 publications found

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]

ENSG00000298549 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016083.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	NM_016083.6	MANE Select	c.*2394A>G		3_prime_UTR	Exon 2 of 2	NP_057167.2
	CNR1	NM_001160226.3		c.*2394A>G		3_prime_UTR	Exon 3 of 3	NP_001153698.1	P21554-1
	CNR1	NM_001160258.3		c.*2394A>G		3_prime_UTR	Exon 4 of 4	NP_001153730.1	P21554-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.*2394A>G		3_prime_UTR	Exon 2 of 2	ENSP00000358513.2	P21554-1
	CNR1	ENST00000428600.3	TSL:1	c.*2394A>G		3_prime_UTR	Exon 2 of 2	ENSP00000412192.2	P21554-1
	CNR1	ENST00000468898.2	TSL:1	c.*2394A>G		3_prime_UTR	Exon 2 of 2	ENSP00000420188.1	P21554-3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.101 AC: 14 AN: 138

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.153 AC: 11 AN: 72

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.170 AC: 7043 AN: 41542

American (AMR) AF: 0.0757 AC: 1157 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3472

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5188

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4826

European-Finnish (FIN) AF: 0.0679 AC: 721 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6016 AN: 68018

Other (OTH) AF: 0.110 AC: 232 AN: 2112

Alfa AF: 0.104 Hom.: 328

Bravo AF: 0.108

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.6
DANN	Benign	0.74
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12720071;

hg19: chr6-88851181;