chr11-72302312-G-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_030813.6(CLPB):c.1249C>A(p.Arg417Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000105 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
CLPB
NM_030813.6 synonymous
NM_030813.6 synonymous
Scores
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.26
Publications
13 publications found
Genes affected
CLPB (HGNC:30664): (ClpB family mitochondrial disaggregase) This gene belongs to the ATP-ases associated with diverse cellular activities (AAA+) superfamily. Members of this superfamily form ring-shaped homo-hexamers and have highly conserved ATPase domains that are involved in various processes including DNA replication, protein degradation and reactivation of misfolded proteins. All members of this family hydrolyze ATP through their AAA+ domains and use the energy generated through ATP hydrolysis to exert mechanical force on their substrates. In addition to an AAA+ domain, the protein encoded by this gene contains a C-terminal D2 domain, which is characteristic of the AAA+ subfamily of Caseinolytic peptidases to which this protein belongs. It cooperates with Hsp70 in the disaggregation of protein aggregates. Allelic variants of this gene are associated with 3-methylglutaconic aciduria, which causes cataracts and neutropenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
CLPB Gene-Disease associations (from GenCC):
- 3-methylglutaconic aciduria, type VIIBInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- neutropenia, severe congenital, 9, autosomal dominantInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Leigh syndromeInheritance: AR Classification: LIMITED Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
BP4
Computational evidence support a benign effect (REVEL=0.079).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CLPB | NM_030813.6 | c.1249C>A | p.Arg417Arg | synonymous_variant | Exon 11 of 17 | ENST00000294053.9 | NP_110440.1 | |
| CLPB | NM_001258392.3 | c.1159C>A | p.Arg387Arg | synonymous_variant | Exon 10 of 16 | ENST00000538039.6 | NP_001245321.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CLPB | ENST00000294053.9 | c.1249C>A | p.Arg417Arg | synonymous_variant | Exon 11 of 17 | 1 | NM_030813.6 | ENSP00000294053.3 | ||
| CLPB | ENST00000538039.6 | c.1159C>A | p.Arg387Arg | synonymous_variant | Exon 10 of 16 | 2 | NM_001258392.3 | ENSP00000441518.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152066
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461804Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727212 show subpopulations
GnomAD4 exome
AF:
AC:
16
AN:
1461804
Hom.:
Cov.:
30
AF XY:
AC XY:
7
AN XY:
727212
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
16
AN:
1111938
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
6
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10
<30
30-35
35-40
40-45
45-50
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>80
Age
GnomAD4 genome 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152066
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74278
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41412
American (AMR)
AF:
AC:
0
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4814
European-Finnish (FIN)
AF:
AC:
0
AN:
10598
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68008
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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