rs806370

Variant names:

• chr6-88146612-C-T
• rs806370
• NM_016083.6:c.-63-1275G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016083.6(CNR1):​c.-63-1275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,238 control chromosomes in the GnomAD database, including 2,160 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 0.14 (2160 hom., cov: 33)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 19 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-1275G>A		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.-63-1275G>A		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21610 AN: 152120 Hom.: 2154 Cov.: 33

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.0853

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.142 AC: 21646 AN: 152238 Hom.: 2160 Cov.: 33 AF XY: 0.148 AC XY: 11013 AN XY: 74442

African (AFR) AF: 0.0887 AC: 3686 AN: 41550

American (AMR) AF: 0.257 AC: 3928 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 647 AN: 3464

East Asian (EAS) AF: 0.505 AC: 2614 AN: 5174

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4828

European-Finnish (FIN) AF: 0.0853 AC: 904 AN: 10604

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8221 AN: 68010

Other (OTH) AF: 0.170 AC: 359 AN: 2108

Alfa AF: 0.133 Hom.: 343

Bravo AF: 0.153

Asia WGS AF: 0.345 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.80
PhyloP100		-1.4
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: rs806370; hg19: chr6-88856331;