1-155235020-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_000157.4(GBA1):ā€‹c.1586A>Gā€‹(p.His529Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 12)
Exomes š‘“: 0.0000025 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GBA1
NM_000157.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94
Variant links:
Genes affected
GBA1 (HGNC:4177): (glucosylceramidase beta 1) This gene encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism. Mutations in this gene cause Gaucher disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides. A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.34169942).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GBA1NM_000157.4 linkuse as main transcriptc.1586A>G p.His529Arg missense_variant 11/11 ENST00000368373.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GBA1ENST00000368373.8 linkuse as main transcriptc.1586A>G p.His529Arg missense_variant 11/111 NM_000157.4 P1P04062-1

Frequencies

GnomAD3 genomes
Cov.:
12
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000255
AC:
2
AN:
785818
Hom.:
0
Cov.:
11
AF XY:
0.00000495
AC XY:
2
AN XY:
403748
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000379
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
12

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Parkinson disease, late-onset Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCentogene AG - the Rare Disease CompanyMar 18, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Benign
20
DANN
Benign
0.90
DEOGEN2
Uncertain
0.56
D;D;.;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.49
N
LIST_S2
Uncertain
0.90
.;D;D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.34
T;T;T;T
MetaSVM
Uncertain
-0.024
T
MutationAssessor
Benign
1.6
L;L;.;.
MutationTaster
Benign
0.63
D;D;D;D;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.59
N;N;N;N
REVEL
Pathogenic
0.66
Sift
Benign
0.41
T;T;T;T
Sift4G
Benign
0.63
T;T;T;T
Polyphen
0.65
P;P;.;.
Vest4
0.38
MutPred
0.64
Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);.;.;
MVP
0.93
MPC
1.1
ClinPred
0.37
T
GERP RS
3.2
Varity_R
0.55
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: chr1-155204811; API