rs12720071

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

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 cumulative frequency of 0.105 (AC=15,960) in the gnomAD database across 152,484 control chromosomes, including 991 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.166. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. 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: 76 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:):

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1662 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_016083.6. You can select a different transcript below to see updated classification 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	Prot: NP_057167.2
	CNR1 NM_001160226.3		c.*2394A>G	3_prime_UTR	Exon 3 of 3	Prot: NP_001153698.1 UniProt:
	CNR1 NM_001160258.3		c.*2394A>G	3_prime_UTR	Exon 4 of 4	Prot: NP_001153730.1 UniProt:

CNR1 NM_016083.6

MANE Select

HGVSc / HGVSpc.*2394A>G

Exon rankExon 2 of 2

3_prime_UTR

Prot: NP_057167.2

CNR1 NM_001160226.3

HGVSc / HGVSpc.*2394A>G

Exon rankExon 3 of 3

3_prime_UTR

Prot: NP_001153698.1UniProt: P21554-1

CNR1 NM_001160258.3

HGVSc / HGVSpc.*2394A>G

Exon rankExon 4 of 4

3_prime_UTR

Prot: NP_001153730.1UniProt: P21554-1

Ensembl Transcripts

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

CNR1 ENST00000369501.3

TSL:1MANE Select

HGVSc / HGVSpc.*2394A>G

Exon rankExon 2 of 2

3_prime_UTR

Prot: ENSP00000358513.2UniProt: P21554-1

CNR1 ENST00000428600.3

TSL:1

HGVSc / HGVSpc.*2394A>G

Exon rankExon 2 of 2

3_prime_UTR

Prot: ENSP00000412192.2UniProt: P21554-1

CNR1 ENST00000468898.2

TSL:1

HGVSc / HGVSpc.*2394A>G

Exon rankExon 2 of 2

3_prime_UTR

Prot: ENSP00000420188.1UniProt: P21554-3

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.104	AC:15900	Hom:983	AN:152154	Cov:32
GnomAD4 exome	AF: 0.118	AC:25	Hom:3	AN:212	Cov:0
GnomAD4 genome	AF: 0.105	AC:15935	Hom:988	AN:152272	Cov:32
TOPMed (Bravo)	AF: 0.108	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.108	AC:8138	Hom:474	AN:75448	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.109	AC:255	Hom:8	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.00478	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0967	AC:29	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.0460	AC:159	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.00525	AC:38	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.0739	AC:13	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.00206	AC:253	Hom:2	AN:122774	Cov:
Turkish Variome	AF: 0.0705	AC:109	Hom:1	AN:1546	Cov:
UK10K	AF: 0.0899	AC:680	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.00413	AC:37	Hom:0	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.0627	1424	22726	0.0284	829	29190

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	13
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.6
DANN	Benign	0.74
GPN-Star LLR	N/A	-3.0
GPN-Star score	N/A	3.0
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	1.8

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs12720071;

hg19: chr6-88851181;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar