ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1077+15C>T

gnomAD frequency: 0.00041  dbSNP: rs202237278
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen RCV001126555 SCV002576742 likely benign Very long chain acyl-CoA dehydrogenase deficiency 2022-09-23 reviewed by expert panel curation The c.1077+15 C>T variant in ACADVL is an intronic variant which falls downstream of the exon 10 3' splice site. The highest population minor allele frequency in gnomAD v2.1.1 is 0.003767 in the Ashkenazi Jewish population with two homozygotes, which is higher than the ClinGen ACADVL VCEP threshold (>0.0035) for BS1, and therefore meets this criterion (BS1). One individual with this variant did display elevated C14:1 levels on newborn screening, however no values were specified. This same individual was compound heterozygous for this variant and two other variants, though the lack of confirmation in trans disallows this evidence from meeting BP2 (PMID: 27246109; Variants: p.Lys187Glu, c.1678+23 C>T). The results from two in silico splicing predictors (NNSPLICE, SpliceAI) support that this variant does not affect splicing (BP4). In summary, this variant meets the criteria to be classified as likely benign for VLCAD deficiency in an autosomal recessive manner based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL VCEP: BS1; BP4. Pilot Specifications; Approved on 08/11/2020.
GeneDx RCV000614488 SCV000719162 likely benign not specified 2017-09-01 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina RCV001126555 SCV001285768 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV001126555 SCV001365182 benign Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1077+15C>T (NP_000009.1:p.?) [GRCH38: NC_000017.11:g.7222880C>T] 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
Invitae RCV001126555 SCV001725279 benign Very long chain acyl-CoA dehydrogenase deficiency 2024-01-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001126555 SCV002088778 likely benign Very long chain acyl-CoA dehydrogenase deficiency 2020-02-03 no assertion criteria provided clinical testing

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