6-88145494-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2135 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	NM_016083.6	MANE Select	c.-63-157T>C		intron	N/A	NP_057167.2
	CNR1	NM_001160226.3		c.-63-157T>C		intron	N/A	NP_001153698.1	P21554-1
	CNR1	NM_001160258.3		c.-63-157T>C		intron	N/A	NP_001153730.1	P21554-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.-63-157T>C		intron	N/A	ENSP00000358513.2	P21554-1
	CNR1	ENST00000428600.3	TSL:1	c.-63-157T>C		intron	N/A	ENSP00000412192.2	P21554-1
	CNR1	ENST00000369499.3	TSL:5	c.-63-157T>C		intron	N/A	ENSP00000358511.2	P21554-1

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

African (AFR) AF: 0.0483 AC: 529 AN: 10946

American (AMR) AF: 0.00307 AC: 39 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: 0.0000334 AC: 1 AN: 29984

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

Middle Eastern (MID) AF: 0.00177 AC: 3 AN: 1694

European-Non Finnish (NFE) AF: 0.0000218 AC: 5 AN: 229850

Other (OTH) AF: 0.00260 AC: 58 AN: 22278

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

African (AFR) AF: 0.0498 AC: 2071 AN: 41564

American (AMR) AF: 0.00255 AC: 39 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00475 Hom.: 7

Bravo AF: 0.0160

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.74
PhyloP100		-0.0090
PromoterAI		-0.00060	Neutral
Mutation Taster		=100/0	polymorphism

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;