Variant rs2501432 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001841.3(CNR2):c.188A>G(p.Gln63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,492 control chromosomes in the GnomAD database, including 286,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.63 ( 30831 hom., cov: 33)

Exomes 𝑓: 0.59 ( 256031 hom. )

Consequence

CNR2
NM_001841.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.47

Variant links:

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]

CNR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.1362777E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR2	NM_001841.3 link	c.188A>G	p.Gln63Arg	missense_variant	2/2	ENST00000374472.5	NP_001832.1	P34972A0A024RAH7
CNR2	XM_011540629.4 link	c.188A>G	p.Gln63Arg	missense_variant	2/2		XP_011538931.1	P34972A0A024RAH7
CNR2	XM_017000261.3 link	c.188A>G	p.Gln63Arg	missense_variant	3/3		XP_016855750.1	P34972A0A024RAH7
CNR2	XM_047444833.1 link	c.188A>G	p.Gln63Arg	missense_variant	2/2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5 link	c.188A>G	p.Gln63Arg	missense_variant	2/2	1	NM_001841.3	ENSP00000363596.4		P34972

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96089

AN:

151626

Hom.:

30821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.618

GnomAD3 exomes

AF:

0.617

AC:

154394

AN:

250392

Hom.:

48315

AF XY:

0.617

AC XY:

83710

AN XY:

135642

show subpopulations

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:

0.609

GnomAD4 exome

AF:

0.589

AC:

861482

AN:

1461748

Hom.:

256031

Cov.:

AF XY:

0.593

AC XY:

430994

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.765

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:

0.634

AC:

96141

AN:

151744

Hom.:

30831

Cov.:

AF XY:

0.637

AC XY:

47195

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.755

Gnomad4 AMR

AF:

0.641

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.523

Gnomad4 SAS

AF:

0.713

Gnomad4 FIN

AF:

0.575

Gnomad4 NFE

AF:

0.574

Gnomad4 OTH

AF:

0.612

Alfa

AF:

0.577

Hom.:

35892

Bravo

AF:

0.644

TwinsUK

AF:

0.561

AC:

2080

ALSPAC

AF:

0.575

AC:

2215

ESP6500AA

AF:

0.728

AC:

3208

ESP6500EA

AF:

0.550

AC:

4732

ExAC

AF:

0.617

AC:

74927

Asia WGS

AF:

0.630

AC:

2190

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

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.9

DANN

Benign

0.17

DEOGEN2

Benign

0.051

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0000031

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.6

PrimateAI

Benign

0.30

PROVEAN

Benign

1.3

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.010

ClinPred

0.0023

GERP RS

5.1

Varity_R

0.14

gMVP

0.069

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over