Variant rs2229579 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.946C>T(p.His316Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,614,024 control chromosomes in the GnomAD database, including 8,083 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.077 ( 606 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7477 hom. )

Consequence

CNR2
NM_001841.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

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=0.0036177933).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CNR2	NM_001841.3 linkuse as main transcript	c.946C>T	p.His316Tyr	missense_variant	2/2	ENST00000374472.5	NP_001832.1
CNR2	XM_011540629.4 linkuse as main transcript	c.946C>T	p.His316Tyr	missense_variant	2/2		XP_011538931.1
CNR2	XM_017000261.3 linkuse as main transcript	c.946C>T	p.His316Tyr	missense_variant	3/3		XP_016855750.1
CNR2	XM_047444833.1 linkuse as main transcript	c.946C>T	p.His316Tyr	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.946C>T	p.His316Tyr	missense_variant	2/2	1	NM_001841.3	ENSP00000363596	P1

Frequencies

GnomAD3 genomes

AF:

0.0772

AC:

11744

AN:

152046

Hom.:

604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0361

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0951

Gnomad OTH

AF:

0.0819

GnomAD3 exomes

AF:

0.100

AC:

25220

AN:

251462

Hom.:

1503

AF XY:

0.102

AC XY:

13924

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0412

Gnomad NFE exome

AF:

0.0950

Gnomad OTH exome

AF:

0.0927

GnomAD4 exome

AF:

0.0971

AC:

141916

AN:

1461860

Hom.:

7477

Cov.:

AF XY:

0.0980

AC XY:

71259

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.0430

Gnomad4 NFE exome

AF:

0.0963

Gnomad4 OTH exome

AF:

0.0988

GnomAD4 genome

AF:

0.0773

AC:

11756

AN:

152164

Hom.:

606

Cov.:

AF XY:

0.0769

AC XY:

5718

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.207

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.0361

Gnomad4 NFE

AF:

0.0951

Gnomad4 OTH

AF:

0.0900

Alfa

AF:

0.0979

Hom.:

1584

Bravo

AF:

0.0793

TwinsUK

AF:

0.0893

AC:

331

ALSPAC

AF:

0.0939

AC:

362

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.0999

AC:

859

ExAC

AF:

0.0972

AC:

11806

Asia WGS

AF:

0.170

AC:

591

AN:

3478

EpiCase

AF:

0.101

EpiControl

AF:

0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.23

DANN

Benign

0.65

DEOGEN2

Benign

0.051

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.050

REVEL

Benign

0.016

Sift

Benign

0.14

Sift4G

Benign

0.40

Polyphen

0.30

Vest4

0.020

ClinPred

0.0025

GERP RS

0.73

Varity_R

0.073

gMVP

0.13

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