chr6-88143916-C-T

Variant names:

• chr6-88143916-C-T
• rs1049353
• NM_016083.6:c.1359G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016083.6(CNR1):​c.1359G>A​(p.Thr453Thr) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 281 publications found

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]

ENSG00000298549 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016083.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	NM_016083.6	MANE Select	c.1359G>A	p.Thr453Thr	synonymous	Exon 2 of 2	NP_057167.2
	CNR1	NM_001160226.3		c.1359G>A	p.Thr453Thr	synonymous	Exon 3 of 3	NP_001153698.1
	CNR1	NM_001160258.3		c.1359G>A	p.Thr453Thr	synonymous	Exon 4 of 4	NP_001153730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.1359G>A	p.Thr453Thr	synonymous	Exon 2 of 2	ENSP00000358513.2
	CNR1	ENST00000428600.3	TSL:1	c.1359G>A	p.Thr453Thr	synonymous	Exon 2 of 2	ENSP00000412192.2
	CNR1	ENST00000468898.2	TSL:1	c.1260G>A	p.Thr420Thr	synonymous	Exon 2 of 2	ENSP00000420188.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29978 AN: 151914 Hom.: 3762 Cov.: 32

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

GnomAD2 exomes AF: 0.214 AC: 53830 AN: 251402 AF XY: 0.218

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 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.: 37 AF XY: 0.258 AC XY: 187962 AN XY: 727218

African (AFR) AF: 0.0499 AC: 1671 AN: 33480

American (AMR) AF: 0.144 AC: 6453 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5249 AN: 26132

East Asian (EAS) AF: 0.0693 AC: 2751 AN: 39694

South Asian (SAS) AF: 0.178 AC: 15371 AN: 86254

European-Finnish (FIN) AF: 0.313 AC: 16747 AN: 53420

Middle Eastern (MID) AF: 0.121 AC: 699 AN: 5768

European-Non Finnish (NFE) AF: 0.286 AC: 318176 AN: 1111962

Other (OTH) AF: 0.233 AC: 14043 AN: 60394

GnomAD4 genome AF: 0.197 AC: 29965 AN: 152034 Hom.: 3758 Cov.: 32 AF XY: 0.195 AC XY: 14512 AN XY: 74320

African (AFR) AF: 0.0635 AC: 2635 AN: 41502

American (AMR) AF: 0.178 AC: 2717 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3468

East Asian (EAS) AF: 0.0693 AC: 357 AN: 5154

South Asian (SAS) AF: 0.173 AC: 834 AN: 4818

European-Finnish (FIN) AF: 0.311 AC: 3276 AN: 10544

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18912 AN: 67952

Other (OTH) AF: 0.165 AC: 348 AN: 2108

Alfa AF: 0.239 Hom.: 17191

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.1
DANN	Benign	0.80
PhyloP100		-0.88
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1049353; hg19: chr6-88853635; COSMIC: COSV62987500; COSMIC: COSV62987500;