chr1-23874867-A-G

Variant names:

• chr1-23874867-A-G
• rs4649124
• NM_001841.3:c.751T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001841.3(CNR2):​c.751T>C​(p.Leu251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,680 control chromosomes in the GnomAD database, including 287,047 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 0.63 (31033 hom., cov: 32)
  • Exomes 𝑓: 0.59 (256014 hom.)
• Consequence: CNR2 NM_001841.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=1.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNR2	NM_001841.3	c.751T>C	p.Leu251Leu	synonymous_variant	Exon 2 of 2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4	c.751T>C	p.Leu251Leu	synonymous_variant	Exon 2 of 2		XP_011538931.1
CNR2	XM_017000261.3	c.751T>C	p.Leu251Leu	synonymous_variant	Exon 3 of 3		XP_016855750.1
CNR2	XM_047444833.1	c.751T>C	p.Leu251Leu	synonymous_variant	Exon 2 of 2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5	c.751T>C	p.Leu251Leu	synonymous_variant	Exon 2 of 2	1	NM_001841.3	ENSP00000363596.4

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96460 AN: 151960 Hom.: 31023 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.619

GnomAD3 exomes AF: 0.617 AC: 154778 AN: 250904 Hom.: 48417 AF XY: 0.617 AC XY: 83683 AN XY: 135606

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.686

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.528

Gnomad SAS exome AF: 0.717

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.589 AC: 861396 AN: 1461602 Hom.: 256014 Cov.: 56 AF XY: 0.593 AC XY: 430959 AN XY: 727092

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.569

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.635 AC: 96512 AN: 152078 Hom.: 31033 Cov.: 32 AF XY: 0.638 AC XY: 47417 AN XY: 74344

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.613

Alfa AF: 0.592 Hom.: 35507

Bravo AF: 0.644

Asia WGS AF: 0.632 AC: 2197 AN: 3478

EpiCase AF: 0.578

EpiControl AF: 0.590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.0
DANN	Benign	0.72

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: rs4649124; hg19: chr1-24201357;