6-88144019-G-T

Variant names:

• chr6-88144019-G-T
• rs78783387
• NM_016083.6:c.1256C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016083.6(CNR1):​c.1256C>A​(p.Ala419Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000266 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: CNR1 NM_016083.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• Publications: 8 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09057805).
• BS2: High AC in GnomAd4 at 52 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	NM_016083.6	MANE Select	c.1256C>A	p.Ala419Glu	missense	Exon 2 of 2	NP_057167.2
	CNR1	NM_001160226.3		c.1256C>A	p.Ala419Glu	missense	Exon 3 of 3	NP_001153698.1	P21554-1
	CNR1	NM_001160258.3		c.1256C>A	p.Ala419Glu	missense	Exon 4 of 4	NP_001153730.1	P21554-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.1256C>A	p.Ala419Glu	missense	Exon 2 of 2	ENSP00000358513.2	P21554-1
	CNR1	ENST00000428600.3	TSL:1	c.1256C>A	p.Ala419Glu	missense	Exon 2 of 2	ENSP00000412192.2	P21554-1
	CNR1	ENST00000468898.2	TSL:1	c.1157C>A	p.Ala386Glu	missense	Exon 2 of 2	ENSP00000420188.1	P21554-3

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152054 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.000366 AC: 92 AN: 251480 AF XY: 0.000316

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.000580

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000259 AC: 378 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.000285 AC XY: 207 AN XY: 727248

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000291 AC: 324 AN: 1112012

Other (OTH) AF: 0.000199 AC: 12 AN: 60396

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152054 Hom.: 0 Cov.: 32 AF XY: 0.000377 AC XY: 28 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.000262 AC: 4 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68020

Other (OTH) AF: 0.000959 AC: 2 AN: 2086

Alfa AF: 0.000478 Hom.: 0

Bravo AF: 0.000302

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000379 AC: 46

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		4.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.21
Sift	Uncertain	0.021	D
Sift4G	Benign	0.89	T
Polyphen		0.024	B
Vest4		0.34
MVP		0.57
ClinPred		0.055	T
GERP RS		5.9
Varity_R		0.17
gMVP		0.72
Mutation Taster		=54/46	polymorphism

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: rs78783387; hg19: chr6-88853738;