Variant: NM_000018.4(ACADVL):c.753-27C>T

CA8337840

474903 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 2272214a-c925-4291-a498-d680d9794a11

Approved on: 2024-09-24

Published on: 2024-09-24

HGVS expressions

NM_000018.4:c.753-27C>T
NM_000018.4(ACADVL):c.753-27C>T
NC_000017.11:g.7222150C>T
CM000679.2:g.7222150C>T
NC_000017.10:g.7125469C>T
CM000679.1:g.7125469C>T
NC_000017.9:g.7066193C>T
NG_007975.1:g.7317C>T
NG_008391.2:g.2901G>A
ENST00000356839.10:c.753-27C>T
ENST00000322910.9:c.*708-27C>T
ENST00000350303.9:c.687-27C>T
ENST00000356839.9:c.753-27C>T
ENST00000543245.6:c.822-27C>T
ENST00000577191.5:n.898C>T
ENST00000581378.5:c.471-27C>T
ENST00000582379.1:n.137-27C>T
NM_000018.3:c.753-27C>T
NM_001033859.2:c.687-27C>T
NM_001270447.1:c.822-27C>T
NM_001270448.1:c.525-27C>T
NM_001033859.3:c.687-27C>T
NM_001270447.2:c.822-27C>T
NM_001270448.2:c.525-27C>T

Likely Benign

• Met criteria codes: BS1 BP4

• Not Met criteria codes: PP4

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.753-27C>T variant in ACADVL is an intronic variant which occurs in intron 8. The highest population minor allele frequency in gnomAD v4.1 is 0.0036 in non-Finnish European population, which is higher than the ClinGen ACADVL Variant Curation Expert Panel threshold (≥0.0035) for BS1, and therefore meets this criterion (BS1). The computational splicing predictor SpliceAI gives a score of 0.14 for acceptor loss suggesting that the variant has no impact on splicing (BP4). At least one individual with this variant was identified by newborn screen, but this information is insufficient to use toward classification (PMID: 27246109). 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: BS1, BP4. (ACADVL VCEP specifications version 1; approved November 9, 2021).

Met criteria codes

• BS1: .0036% NFE. v4.1
• BP4: Splice AI change >.2. No change NNSplice, MaxEntScan

Not Met criteria codes

• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline