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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000018.4(ACADVL):c.128G>A (p.Gly43Asp)

CA341517

21015 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9f8832bb-a666-4dd7-b38a-df471b3b5691

HGVS expressions

NM_000018.4:c.128G>A

NM_000018.4(ACADVL):c.128G>A (p.Gly43Asp)

NC_000017.11:g.7220187G>A

CM000679.2:g.7220187G>A

NC_000017.10:g.7123506G>A

CM000679.1:g.7123506G>A

NC_000017.9:g.7064230G>A

NG_007975.1:g.5354G>A

NG_008391.2:g.4864C>T

ENST00000356839.10:c.128G>A

ENST00000322910.9:c.*83G>A

ENST00000350303.9:c.128G>A

ENST00000356839.9:c.128G>A

ENST00000543245.6:c.197G>A

ENST00000577191.5:n.205G>A

ENST00000577857.5:n.218G>A

ENST00000578269.5:n.235G>A

ENST00000578421.1:n.262G>A

ENST00000579286.5:n.235G>A

ENST00000579886.2:c.128G>A

ENST00000580263.5:n.218G>A

ENST00000581562.5:n.175G>A

ENST00000582056.5:n.218G>A

ENST00000582356.5:n.253G>A

ENST00000583312.5:c.128G>A

ENST00000584103.5:c.128G>A

NM_000018.3:c.128G>A

NM_001033859.2:c.128G>A

NM_001270447.1:c.197G>A

NM_001270448.1:c.-101G>A

NM_001033859.3:c.128G>A

NM_001270447.2:c.197G>A

NM_001270448.2:c.-101G>A

Benign

BP2 BP4 BA1

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.128G>A variant in ACADVL is well characterized as a benign polymorphism, being present in several VLCAD cases with alternate pathogenic variants (BP2; PMIDs: 11914034, 15210884, more in literature). The highest population minor allele frequency in gnomAD v2.1.1 is 0.17 in the East Asian population, which is higher than the ClinGen ACADVL Variant Curation Expert Panel threshold (≥0.007) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.259, which is below the threshold of 0.5, evidence that does not predict a damaging effect on ACADVL function (BP4). In summary, this variant meets criteria to be classified as benign for very long chain acyl-CoA dehydrogenase deficiency in an autosomal recessive manner. ACADVL-specific ACMG/AMP criteria applied: BA1; BP2; BP4

BP2

This variant is seen in-cis with pathogenic variants in both heterozygous and homozygous states in many different reported probands.

BP4

REVEL score of 0.259

BA1

gnomAD frequency of 0.17004 in East Asian population with 162 homozygotes

Approved on: 2022-09-22

Published on: 2022-09-22

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.