rs806374

Variant names:

• chr6-88147601-T-C
• rs806374
• NM_016083.6:c.-63-2264A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-88147601-T-C
• chr6-88147601-T-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.-63-2264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,040 control chromosomes in the GnomAD database, including 10,715 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 0.37 (10714 hom., cov: 32)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 27 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-2264A>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.-63-2264A>G		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56439 AN: 151892 Hom.: 10685 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.300 AC: 9 AN: 30 Hom.: 1 AF XY: 0.227 AC XY: 5 AN XY: 22

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.273 AC: 6 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.372 AC: 56523 AN: 152010 Hom.: 10714 Cov.: 32 AF XY: 0.372 AC XY: 27640 AN XY: 74310

African (AFR) AF: 0.419 AC: 17393 AN: 41466

American (AMR) AF: 0.397 AC: 6068 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2652 AN: 5152

South Asian (SAS) AF: 0.334 AC: 1614 AN: 4826

European-Finnish (FIN) AF: 0.289 AC: 3057 AN: 10560

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23051 AN: 67934

Other (OTH) AF: 0.379 AC: 802 AN: 2114

Alfa AF: 0.353 Hom.: 38775

Bravo AF: 0.381

Asia WGS AF: 0.430 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.45
PhyloP100		-2.3
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: rs806374; hg19: chr6-88857320;