NM_016083.6:c.-63-6514A>G

Variant names:

• chr6-88151851-T-C
• rs6454672
• NM_016083.6:c.-63-6514A>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.-63-6514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,018 control chromosomes in the GnomAD database, including 2,787 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 0.17 (2787 hom., cov: 31)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-6514A>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.-63-6514A>G		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25803 AN: 151902 Hom.: 2781 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.170 AC: 25822 AN: 152018 Hom.: 2787 Cov.: 31 AF XY: 0.165 AC XY: 12267 AN XY: 74324

African (AFR) AF: 0.307 AC: 12722 AN: 41440

American (AMR) AF: 0.120 AC: 1837 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3470

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5172

South Asian (SAS) AF: 0.0940 AC: 452 AN: 4810

European-Finnish (FIN) AF: 0.106 AC: 1117 AN: 10544

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8656 AN: 67982

Other (OTH) AF: 0.155 AC: 327 AN: 2110

Alfa AF: 0.151 Hom.: 576

Bravo AF: 0.178

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		-0.51
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: rs6454672; hg19: chr6-88861570;