rs6454673

Variant names:

• chr6-88161330-G-A
• rs6454673
• NM_016083.6:c.-64+4473C>T

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+4473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,996 control chromosomes in the GnomAD database, including 6,834 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 0.30 (6834 hom., cov: 32)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 8 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-64+4473C>T		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+4473C>T		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45068 AN: 151878 Hom.: 6824 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.297 AC: 45104 AN: 151996 Hom.: 6834 Cov.: 32 AF XY: 0.296 AC XY: 21979 AN XY: 74266

African (AFR) AF: 0.330 AC: 13681 AN: 41452

American (AMR) AF: 0.230 AC: 3520 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3464

East Asian (EAS) AF: 0.210 AC: 1087 AN: 5170

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4816

European-Finnish (FIN) AF: 0.324 AC: 3409 AN: 10526

Middle Eastern (MID) AF: 0.372 AC: 108 AN: 290

European-Non Finnish (NFE) AF: 0.299 AC: 20323 AN: 67968

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.290 Hom.: 11106

Bravo AF: 0.291

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		2.1
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: rs6454673; hg19: chr6-88871049;