chr1-23875421-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001841.3(CNR2):c.197G>A(p.Arg66Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,198 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0094 ( 27 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 19 hom. )
Consequence
CNR2
NM_001841.3 missense
NM_001841.3 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.552
Genes affected
CNR2 (HGNC:2160): (cannabinoid receptor 2) The cannabinoid delta-9-tetrahydrocannabinol is the principal psychoactive ingredient of marijuana. The proteins encoded by this gene and the cannabinoid receptor 1 (brain) (CNR1) gene have the characteristics of a guanine nucleotide-binding protein (G-protein)-coupled receptor for cannabinoids. They inhibit adenylate cyclase activity in a dose-dependent, stereoselective, and pertussis toxin-sensitive manner. These proteins have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. The cannabinoid receptors are members of family 1 of the G-protein-coupled receptors. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004694581).
BP6
?
Variant 1-23875421-C-T is Benign according to our data. Variant chr1-23875421-C-T is described in ClinVar as [Benign]. Clinvar id is 785933.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00939 (1431/152326) while in subpopulation AFR AF= 0.0309 (1284/41590). AF 95% confidence interval is 0.0295. There are 27 homozygotes in gnomad4. There are 706 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 28 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNR2 | NM_001841.3 | c.197G>A | p.Arg66Gln | missense_variant | 2/2 | ENST00000374472.5 | |
CNR2 | XM_011540629.4 | c.197G>A | p.Arg66Gln | missense_variant | 2/2 | ||
CNR2 | XM_017000261.3 | c.197G>A | p.Arg66Gln | missense_variant | 3/3 | ||
CNR2 | XM_047444833.1 | c.197G>A | p.Arg66Gln | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNR2 | ENST00000374472.5 | c.197G>A | p.Arg66Gln | missense_variant | 2/2 | 1 | NM_001841.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00938 AC: 1427AN: 152208Hom.: 28 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00298 AC: 747AN: 250902Hom.: 14 AF XY: 0.00228 AC XY: 310AN XY: 135810
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GnomAD4 exome AF: 0.00128 AC: 1871AN: 1461872Hom.: 19 Cov.: 68 AF XY: 0.00116 AC XY: 844AN XY: 727232
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GnomAD4 genome ? AF: 0.00939 AC: 1431AN: 152326Hom.: 27 Cov.: 33 AF XY: 0.00948 AC XY: 706AN XY: 74476
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at