6-88164009-T-C

Variant names:

• chr6-88164009-T-C
• rs11756397
• NM_016083.6:c.-64+1794A>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.-64+1794A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,200 control chromosomes in the GnomAD database, including 2,945 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 0.19 (2945 hom., cov: 33)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 2 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	NM_016083.6	MANE Select	c.-64+1794A>G		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-207+1794A>G		intron	N/A	NP_001153698.1
	CNR1	NM_001160258.3		c.-207+248A>G		intron	N/A	NP_001153730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.-64+1794A>G		intron	N/A	ENSP00000358513.2
	CNR1	ENST00000369499.3	TSL:5	c.-64+248A>G		intron	N/A	ENSP00000358511.2
	CNR1	ENST00000551417.2	TSL:5	c.-207+248A>G		intron	N/A	ENSP00000446702.2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28899 AN: 152082 Hom.: 2941 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.190 AC: 28911 AN: 152200 Hom.: 2945 Cov.: 33 AF XY: 0.191 AC XY: 14246 AN XY: 74410

African (AFR) AF: 0.140 AC: 5802 AN: 41522

American (AMR) AF: 0.170 AC: 2601 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3466

East Asian (EAS) AF: 0.171 AC: 887 AN: 5190

South Asian (SAS) AF: 0.205 AC: 987 AN: 4822

European-Finnish (FIN) AF: 0.241 AC: 2552 AN: 10584

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14941 AN: 67996

Other (OTH) AF: 0.216 AC: 457 AN: 2114

Alfa AF: 0.213 Hom.: 717

Bravo AF: 0.181

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		-0.36
PromoterAI		0.0052	Neutral
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

Other links and lift over

dbSNP: rs11756397; hg19: chr6-88873728; COSMIC: COSV107469425; COSMIC: COSV107469425;