Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000018.4(ACADVL):c.478-22_478-21del

CA8337734

254701 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b3cca74a-9b5b-460c-b3e5-6ccdad365926

HGVS expressions

NM_000018.4:c.478-22_478-21del

NM_000018.4(ACADVL):c.478-22_478-21del

NC_000017.11:g.7221516_7221517del

CM000679.2:g.7221516_7221517del

NC_000017.10:g.7124835_7124836del

CM000679.1:g.7124835_7124836del

NC_000017.9:g.7065559_7065560del

NG_007975.1:g.6683_6684del

NG_008391.2:g.3534_3535del

ENST00000356839.10:c.478-22_478-21del

ENST00000322910.9:c.*433-22_*433-21del

ENST00000350303.9:c.412-22_412-21del

ENST00000356839.9:c.478-22_478-21del

ENST00000543245.6:c.547-22_547-21del

ENST00000577191.5:n.555-22_555-21del

ENST00000577433.5:n.686-22_686-21del

ENST00000577857.5:n.294-22_294-21del

ENST00000579286.5:n.659-22_659-21del

ENST00000579886.2:c.316-22_316-21del

ENST00000580365.1:n.209-22_209-21del

ENST00000581378.5:n.177-3_177-2del

ENST00000581562.5:n.525-436_525-435del

ENST00000582166.1:n.459-22_459-21del

ENST00000583312.5:c.478-22_478-21del

ENST00000583760.1:n.238_239del

NM_000018.3:c.478-22_478-21del

NM_001033859.2:c.412-22_412-21del

NM_001270447.1:c.547-22_547-21del

NM_001270448.1:c.250-22_250-21del

NM_001033859.3:c.412-22_412-21del

NM_001270447.2:c.547-22_547-21del

NM_001270448.2:c.250-22_250-21del

Benign

BA1

BP4

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

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.

BA1

MAF is 0.22535 in African population, with 620 homozygotes

BP4

The variant in SpliceAI has an acceptor loss delta score of 0.22 at -12 bp with the "raw" setting, however this seems to be weakening an unannotated splice-site. Consider whether to use "masked" setting instead for variant interpretation. NNsplice predicts no change in splicing.

Approved on: 2022-09-22

Published on: 2022-09-22

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