6-88145494-A-G

Position:

• chr6-88145494-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016083.6(CNR1):​c.-63-157T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00527 in 526,092 control chromosomes in the GnomAD database, including 84 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 0.014 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (21 hom.)
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2135/152324) while in subpopulation AFR AF= 0.0498 (2071/41564). AF 95% confidence interval is 0.048. There are 63 homozygotes in gnomad4. There are 972 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2135 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-157T>C		intron_variant		ENST00000369501.3	NP_057167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR1	ENST00000369501.3	c.-63-157T>C		intron_variant		1	NM_016083.6	ENSP00000358513.2
CNR1	ENST00000428600.3	c.-63-157T>C		intron_variant		1		ENSP00000412192.2
CNR1	ENST00000369499.3	c.-63-157T>C		intron_variant		5		ENSP00000358511.2
CNR1	ENST00000551417.2	c.-63-157T>C		intron_variant		5		ENSP00000446702.2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2132 AN: 152206 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00170 AC: 635 AN: 373768 Hom.: 21 AF XY: 0.00142 AC XY: 275 AN XY: 194278

Gnomad4 AFR exome AF: 0.0483

Gnomad4 AMR exome AF: 0.00307

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000334

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000218

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.0140 AC: 2135 AN: 152324 Hom.: 63 Cov.: 32 AF XY: 0.0131 AC XY: 972 AN XY: 74470

Gnomad4 AFR AF: 0.0498

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00282 Hom.: 4

Bravo AF: 0.0160

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs16880261; hg19: chr6-88855213;