rs16828926

Positions:

• chr1-23888640-G-A
• chr1-23888640-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR2	NM_001841.3	c.-45-12978C>T		intron_variant		ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.-310C>T		5_prime_UTR_variant	1/2		XP_011538931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.-45-12978C>T		intron_variant		1	NM_001841.3	ENSP00000363596	P1

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

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.132

Alfa AF: 0.141 Hom.: 1591

Bravo AF: 0.120

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.95
DANN	Benign	0.55

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: rs16828926; hg19: chr1-24215130;