rs60400822
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000018.4(ACADVL):c.478-22_478-21del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,613,924 control chromosomes in the GnomAD database, including 2,057 homozygotes. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.065 ( 1057 hom., cov: 31)
Exomes 𝑓: 0.0078 ( 1000 hom. )
Consequence
ACADVL
NM_000018.4 intron
NM_000018.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.514
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 17-7221515-CCA-C is Benign according to our data. Variant chr17-7221515-CCA-C is described in ClinVar as [Benign]. Clinvar id is 254701.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADVL | NM_000018.4 | c.478-22_478-21del | intron_variant | ENST00000356839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADVL | ENST00000356839.10 | c.478-22_478-21del | intron_variant | 1 | NM_000018.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0649 AC: 9861AN: 152026Hom.: 1049 Cov.: 31
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GnomAD3 exomes AF: 0.0181 AC: 4552AN: 251378Hom.: 399 AF XY: 0.0136 AC XY: 1854AN XY: 135892
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GnomAD4 exome AF: 0.00778 AC: 11379AN: 1461780Hom.: 1000 AF XY: 0.00692 AC XY: 5032AN XY: 727194
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GnomAD4 genome ? AF: 0.0651 AC: 9900AN: 152144Hom.: 1057 Cov.: 31 AF XY: 0.0624 AC XY: 4642AN XY: 74378
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Very long chain acyl-CoA dehydrogenase deficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Nov 01, 2019 | The NM_000018.3:c.478-22_478-21delCA (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7221516_7221517delCA] variant in ACADVL gene is interpretated to be Benign based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: BS1, BS2 - |
Benign, reviewed by expert panel | curation | ClinGen ACADVL Variant Curation Expert Panel, ClinGen | Sep 22, 2022 | The c.478-22_478-21del variant in ACADVL is an intronic variant which occurs in intron 6. The highest population minor allele frequency in gnomAD v2.1.1 is 0.2253 in the African population, which is higher than the ClinGen ACADVL Variant Curation Expert Panel threshold (≥0.007) for BA1, and therefore meets this criterion (BA1). The results from in silico splicing predictors (SpliceAI) support that this variant does not affect splicing (BP4). In summary, this variant meets the criteria to be classified as benign for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: BA1, BP4. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 13, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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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