Variant 1-23875221-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001841.3(CNR2):c.397C>A(p.Leu133Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,614,172 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 30 hom. )

Consequence

CNR2
NM_001841.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.742

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009951115).

BS2

High Homozygotes in GnomAdExome4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR2	NM_001841.3 linkuse as main transcript	c.397C>A	p.Leu133Ile	missense_variant	2/2	ENST00000374472.5	NP_001832.1	P34972A0A024RAH7
CNR2	XM_011540629.4 linkuse as main transcript	c.397C>A	p.Leu133Ile	missense_variant	2/2		XP_011538931.1	P34972A0A024RAH7
CNR2	XM_017000261.3 linkuse as main transcript	c.397C>A	p.Leu133Ile	missense_variant	3/3		XP_016855750.1	P34972A0A024RAH7
CNR2	XM_047444833.1 linkuse as main transcript	c.397C>A	p.Leu133Ile	missense_variant	2/2		XP_047300789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR2	ENST00000374472.5 linkuse as main transcript	c.397C>A	p.Leu133Ile	missense_variant	2/2	1	NM_001841.3	ENSP00000363596.4		P34972

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

407

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00379

AC:

953

AN:

251154

Hom.:

AF XY:

0.00400

AC XY:

543

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.0177

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00454

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00478

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00450

AC:

6578

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

3254

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00435

Gnomad4 FIN exome

AF:

0.000637

Gnomad4 NFE exome

AF:

0.00480

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152326

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00417

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.00267

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00363

AC:

441

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00502

EpiControl

AF:

0.00516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.064

Eigen

Benign

-0.00059

Eigen_PC

Benign

0.074

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.77

M_CAP

Benign

0.011

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.040

REVEL

Benign

0.11

Sift

Benign

0.98

Sift4G

Benign

0.72

Polyphen

0.88

Vest4

0.079

MVP

0.67

ClinPred

0.039

GERP RS

5.8

Varity_R

0.52

gMVP

0.26

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