6-88151979-A-G

Variant names:

• chr6-88151979-A-G
• rs6928813
• NM_016083.6:c.-63-6642T>C

Variant summary

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

The NM_016083.6(CNR1):​c.-63-6642T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,080 control chromosomes in the GnomAD database, including 3,745 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 0.20 (3745 hom., cov: 31)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 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.-63-6642T>C		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-206-4173T>C		intron	N/A	NP_001153698.1
	CNR1	NM_001160258.3		c.-206-4173T>C		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.-63-6642T>C		intron	N/A	ENSP00000358513.2
	CNR1	ENST00000428600.3	TSL:1	c.-63-6642T>C		intron	N/A	ENSP00000412192.2
	CNR1	ENST00000369499.3	TSL:5	c.-63-6642T>C		intron	N/A	ENSP00000358511.2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31005 AN: 151964 Hom.: 3734 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.204 AC: 31029 AN: 152080 Hom.: 3745 Cov.: 31 AF XY: 0.198 AC XY: 14735 AN XY: 74346

African (AFR) AF: 0.331 AC: 13713 AN: 41448

American (AMR) AF: 0.150 AC: 2290 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3472

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5186

South Asian (SAS) AF: 0.151 AC: 729 AN: 4818

European-Finnish (FIN) AF: 0.128 AC: 1356 AN: 10562

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11633 AN: 67986

Other (OTH) AF: 0.189 AC: 398 AN: 2110

Alfa AF: 0.180 Hom.: 7757

Bravo AF: 0.212

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.15
PhyloP100		1.6
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: rs6928813; hg19: chr6-88861698;