rs786204713
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000018.4(ACADVL):c.298_299delCA(p.Gln100ValfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
ACADVL
NM_000018.4 frameshift
NM_000018.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.67
Publications
2 publications found
Genes affected
ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
ACADVL Gene-Disease associations (from GenCC):
- very long chain acyl-CoA dehydrogenase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-7220782-GAC-G is Pathogenic according to our data. Variant chr17-7220782-GAC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 189116.Status of the report is reviewed_by_expert_panel, 3 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000018.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACADVL | MANE Select | c.298_299delCA | p.Gln100ValfsTer3 | frameshift | Exon 5 of 20 | NP_000009.1 | P49748-1 | ||
| ACADVL | c.367_368delCA | p.Gln123ValfsTer3 | frameshift | Exon 6 of 21 | NP_001257376.1 | P49748-3 | |||
| ACADVL | c.232_233delCA | p.Gln78ValfsTer3 | frameshift | Exon 4 of 19 | NP_001029031.1 | P49748-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACADVL | TSL:1 MANE Select | c.298_299delCA | p.Gln100ValfsTer3 | frameshift | Exon 5 of 20 | ENSP00000349297.5 | P49748-1 | ||
| ACADVL | TSL:1 | c.232_233delCA | p.Gln78ValfsTer3 | frameshift | Exon 4 of 19 | ENSP00000344152.5 | P49748-2 | ||
| ACADVL | TSL:2 | c.367_368delCA | p.Gln123ValfsTer3 | frameshift | Exon 6 of 21 | ENSP00000438689.2 | P49748-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461780Hom.: 0 AF XY: 0.00000963 AC XY: 7AN XY: 727180 show subpopulations
GnomAD4 exome
AF:
AC:
12
AN:
1461780
Hom.:
AF XY:
AC XY:
7
AN XY:
727180
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
1
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
AC:
0
AN:
53328
Middle Eastern (MID)
AF:
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
9
AN:
1112004
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:reviewed by expert panel
Pathogenic
VUS
Benign
Condition
7
-
-
Very long chain acyl-CoA dehydrogenase deficiency (7)
2
-
-
not provided (2)
1
-
-
ACADVL-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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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