6-88145192-A-T

Position:

• chr6-88145192-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016083.6(CNR1):​c.83T>A​(p.Ile28Asn) variant causes a missense change. 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNR1	NM_016083.6	c.83T>A	p.Ile28Asn	missense_variant	2/2	ENST00000369501.3	NP_057167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNR1	ENST00000369501.3	c.83T>A	p.Ile28Asn	missense_variant	2/2	1	NM_016083.6	ENSP00000358513.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.83T>A (p.I28N) alteration is located in exon 2 (coding exon 1) of the CNR1 gene. This alteration results from a T to A substitution at nucleotide position 83, causing the isoleucine (I) at amino acid position 28 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T;T;T;.;T;.
Eigen	Benign	0.082
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	.;.;.;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T
MetaSVM	Benign	-0.70	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.44	N;N;N;D;N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.023	D;D;D;D;D;D
Sift4G	Uncertain	0.024	D;D;D;D;D;D
Polyphen		0.41	B;B;B;.;B;.
Vest4		0.49
MutPred		0.41		Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);Gain of disorder (P = 0.0235);
MVP		0.87
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.37
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-88854911;