6-88145494-A-C

Variant names:

• chr6-88145494-A-C
• rs16880261
• NM_016083.6:c.-63-157T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016083.6(CNR1):​c.-63-157T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNR1 NM_016083.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR1	NM_016083.6	c.-63-157T>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.-63-157T>G		intron_variant	Intron 1 of 1	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 373770 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 194278

African (AFR) AF: 0.00 AC: 0 AN: 10948

American (AMR) AF: 0.00 AC: 0 AN: 12706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12036

East Asian (EAS) AF: 0.00 AC: 0 AN: 27218

South Asian (SAS) AF: 0.00 AC: 0 AN: 29984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 229850

Other (OTH) AF: 0.00 AC: 0 AN: 22278

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		-0.0090
PromoterAI		0.018	Neutral

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: rs16880261; hg19: chr6-88855213;