6-88158206-T-C

Variant names:

• chr6-88158206-T-C
• rs12205430
• NM_016083.6:c.-64+7597A>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+7597A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,230 control chromosomes in the GnomAD database, including 2,438 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 0.16 (2438 hom., cov: 33)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-64+7597A>G		intron_variant	Intron 1 of 1	ENST00000369501.3	NP_057167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR1	ENST00000369501.3	c.-64+7597A>G		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23907 AN: 152112 Hom.: 2439 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.157 AC: 23899 AN: 152230 Hom.: 2438 Cov.: 33 AF XY: 0.159 AC XY: 11802 AN XY: 74414

African (AFR) AF: 0.0369 AC: 1533 AN: 41570

American (AMR) AF: 0.143 AC: 2187 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3468

East Asian (EAS) AF: 0.161 AC: 835 AN: 5178

South Asian (SAS) AF: 0.187 AC: 901 AN: 4822

European-Finnish (FIN) AF: 0.214 AC: 2271 AN: 10588

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14873 AN: 68006

Other (OTH) AF: 0.196 AC: 414 AN: 2116

Alfa AF: 0.195 Hom.: 10197

Bravo AF: 0.145

Asia WGS AF: 0.169 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.42
PhyloP100		-1.5
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: rs12205430; hg19: chr6-88867925;