1-23888640-G-A

Variant names:

• chr1-23888640-G-A
• rs16828926
• NM_001841.3:c.-45-12978C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001841.3(CNR2):​c.-45-12978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,026 control chromosomes in the GnomAD database, including 1,361 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 0.12 (1361 hom., cov: 31)
• Consequence: CNR2 NM_001841.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 6 publications found

Genes affected

CNR2 (HGNC:2160): (cannabinoid receptor 2) The cannabinoid delta-9-tetrahydrocannabinol is the principal psychoactive ingredient of marijuana. The proteins encoded by this gene and the cannabinoid receptor 1 (brain) (CNR1) gene have the characteristics of a guanine nucleotide-binding protein (G-protein)-coupled receptor for cannabinoids. They inhibit adenylate cyclase activity in a dose-dependent, stereoselective, and pertussis toxin-sensitive manner. These proteins have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. The cannabinoid receptors are members of family 1 of the G-protein-coupled receptors. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001841.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	NM_001841.3	MANE Select	c.-45-12978C>T		intron	N/A	NP_001832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR2	ENST00000374472.5	TSL:1 MANE Select	c.-45-12978C>T		intron	N/A	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17993 AN: 151908 Hom.: 1356 Cov.: 31

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.118 AC: 18011 AN: 152026 Hom.: 1361 Cov.: 31 AF XY: 0.118 AC XY: 8739 AN XY: 74314

African (AFR) AF: 0.0436 AC: 1810 AN: 41482

American (AMR) AF: 0.122 AC: 1868 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1706 AN: 5154

South Asian (SAS) AF: 0.158 AC: 757 AN: 4806

European-Finnish (FIN) AF: 0.0762 AC: 808 AN: 10598

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9979 AN: 67956

Other (OTH) AF: 0.132 AC: 279 AN: 2108

Alfa AF: 0.139 Hom.: 2389

Bravo AF: 0.120

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.95
DANN	Benign	0.55
PhyloP100		-0.66
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: rs16828926; hg19: chr1-24215130;