18-11851905-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020412.5(CHMP1B):​c.394A>T​(p.Met132Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

CHMP1B
NM_020412.5 missense

Scores

1
9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.95
Variant links:
Genes affected
CHMP1B (HGNC:24287): (charged multivesicular body protein 1B) CHMP1B belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]
GNAL (HGNC:4388): (G protein subunit alpha L) This gene encodes a stimulatory G protein alpha subunit which mediates odorant signaling in the olfactory epithelium. This protein couples dopamine type 1 receptors and adenosine A2A receptors and is widely expressed in the central nervous system. Mutations in this gene have been associated with dystonia 25 and this gene is located in a susceptibility region for bipolar disorder and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
CHMP1B-AS1 (HGNC:52778): (CHMP1B antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3145793).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHMP1BNM_020412.5 linkc.394A>T p.Met132Leu missense_variant Exon 1 of 1 ENST00000526991.3 NP_065145.2 Q7LBR1
GNALNM_182978.4 linkc.723-10490A>T intron_variant Intron 5 of 11 ENST00000334049.11 NP_892023.1 P38405-2
GNALNM_001369387.1 linkc.492-10490A>T intron_variant Intron 5 of 11 ENST00000423027.8 NP_001356316.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHMP1BENST00000526991.3 linkc.394A>T p.Met132Leu missense_variant Exon 1 of 1 6 NM_020412.5 ENSP00000432279.1 Q7LBR1
GNALENST00000334049.11 linkc.723-10490A>T intron_variant Intron 5 of 11 1 NM_182978.4 ENSP00000334051.5 P38405-2
GNALENST00000423027.8 linkc.492-10490A>T intron_variant Intron 5 of 11 1 NM_001369387.1 ENSP00000408489.2 P38405-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249210
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135206
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
25
DANN
Benign
0.96
DEOGEN2
Uncertain
0.56
D
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.55
T
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.24
Sift
Benign
0.092
T
Sift4G
Benign
0.27
T
Polyphen
0.035
B
Vest4
0.52
MutPred
0.51
Loss of phosphorylation at T135 (P = 0.1618);
MVP
0.95
MPC
0.69
ClinPred
0.68
D
GERP RS
5.6
Varity_R
0.55
gMVP
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775796754; hg19: chr18-11851904; API