Variant 6-88143916-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_016083.6(CNR1):c.1359G>A(p.Thr453=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,862 control chromosomes in the GnomAD database, including 56,313 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 0.20 ( 3758 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52555 hom. )

Consequence

CNR1
NM_016083.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.884

Variant links:

Genes affected

CNR1 (HGNC:2159): (cannabinoid receptor 1) This gene encodes one of two cannabinoid receptors. The cannabinoids, principally delta-9-tetrahydrocannabinol and synthetic analogs, are psychoactive ingredients of marijuana. The cannabinoid receptors are members of the guanine-nucleotide-binding protein (G-protein) coupled receptor family, which inhibit adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. The two receptors have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. Multiple transcript variants encoding two different protein isoforms have been described for this gene. [provided by RefSeq, May 2009]

CNR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-0.884 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNR1	NM_016083.6 linkuse as main transcript	c.1359G>A	p.Thr453=	synonymous_variant	2/2	ENST00000369501.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNR1	ENST00000369501.3 linkuse as main transcript	c.1359G>A	p.Thr453=	synonymous_variant	2/2	1	NM_016083.6	P1	P21554-1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29978

AN:

151914

Hom.:

3762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0637

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0693

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.214

AC:

53830

AN:

251402

Hom.:

6662

AF XY:

0.218

AC XY:

29668

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0573

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.0704

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.261

AC:

381160

AN:

1461828

Hom.:

52555

Cov.:

AF XY:

0.258

AC XY:

187962

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0499

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.0693

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.313

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.197

AC:

29965

AN:

152034

Hom.:

3758

Cov.:

AF XY:

0.195

AC XY:

14512

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0635

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.0693

Gnomad4 SAS

AF:

0.173

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.247

Hom.:

8702

Bravo

AF:

0.180

Asia WGS

AF:

0.105

AC:

363

AN:

3478

EpiCase

AF:

0.258

EpiControl

AF:

0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.1

DANN

Benign

0.80

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