6-88148454-A-AT

Variant names:

• chr6-88148454-A-AT
• rs12720072
• NM_016083.6:c.-63-3118_-63-3117insA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_016083.6(CNR1):​c.-63-3118_-63-3117insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,078 control chromosomes in the GnomAD database, including 3,119 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (3119 hom., cov: 30)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 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.-63-3118_-63-3117insA		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-206-649_-206-648insA		intron	N/A	NP_001153698.1
	CNR1	NM_001160258.3		c.-206-649_-206-648insA		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.-63-3118_-63-3117insA		intron	N/A	ENSP00000358513.2
	CNR1	ENST00000428600.3	TSL:1	c.-63-3118_-63-3117insA		intron	N/A	ENSP00000412192.2
	CNR1	ENST00000369499.3	TSL:5	c.-63-3118_-63-3117insA		intron	N/A	ENSP00000358511.2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24832 AN: 151960 Hom.: 3115 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.164 AC: 24873 AN: 152078 Hom.: 3119 Cov.: 30 AF XY: 0.161 AC XY: 11959 AN XY: 74364

African (AFR) AF: 0.340 AC: 14104 AN: 41444

American (AMR) AF: 0.101 AC: 1552 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3466

East Asian (EAS) AF: 0.321 AC: 1657 AN: 5166

South Asian (SAS) AF: 0.111 AC: 536 AN: 4818

European-Finnish (FIN) AF: 0.0530 AC: 561 AN: 10588

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5379 AN: 67988

Other (OTH) AF: 0.165 AC: 349 AN: 2110

Alfa AF: 0.123 Hom.: 232

Bravo AF: 0.178

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17
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: rs12720072; hg19: chr6-88858173;