6-88144776-T-C

Variant names:

• chr6-88144776-T-C
• rs77016054
• NM_016083.6:c.499A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016083.6(CNR1):​c.499A>G​(p.Ser167Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNR1 NM_016083.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.499A>G	p.Ser167Gly	missense	Exon 2 of 2	NP_057167.2
	CNR1	NM_001160226.3		c.499A>G	p.Ser167Gly	missense	Exon 3 of 3	NP_001153698.1
	CNR1	NM_001160258.3		c.499A>G	p.Ser167Gly	missense	Exon 4 of 4	NP_001153730.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNR1	ENST00000369501.3	TSL:1 MANE Select	c.499A>G	p.Ser167Gly	missense	Exon 2 of 2	ENSP00000358513.2
	CNR1	ENST00000428600.3	TSL:1	c.499A>G	p.Ser167Gly	missense	Exon 2 of 2	ENSP00000412192.2
	CNR1	ENST00000468898.2	TSL:1	c.400A>G	p.Ser134Gly	missense	Exon 2 of 2	ENSP00000420188.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.98	L
PhyloP100		8.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	1.3	N
REVEL	Uncertain	0.34
Sift	Benign	0.15	T
Sift4G	Benign	0.66	T
Polyphen		1.0	D
Vest4		0.73
MVP		0.77
ClinPred		0.87	D
GERP RS		5.8
PromoterAI		-0.025	Neutral
Varity_R		0.41
gMVP		0.95
Mutation Taster		=13/87	disease causing

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: rs77016054; hg19: chr6-88854495; COSMIC: COSV100759175; COSMIC: COSV100759175;