Variant: NM_000018.4(ACADVL):c.1581G>A (p.Pro527=)

CA8338160

324995 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 7c49fb24-6b08-4335-9337-7be0e78ca11f

Approved on: 2025-03-25

Published on: 2025-04-01

HGVS expressions

NM_000018.4:c.1581G>A
NM_000018.4(ACADVL):c.1581G>A (p.Pro527=)
NC_000017.11:g.7224369G>A
CM000679.2:g.7224369G>A
NC_000017.10:g.7127688G>A
CM000679.1:g.7127688G>A
NC_000017.9:g.7068412G>A
NG_007975.1:g.9536G>A
NG_008391.2:g.682C>T
NG_033038.1:g.15176C>T
ENST00000356839.10:c.1581G>A
ENST00000322910.9:c.*1536G>A
ENST00000350303.9:c.1515G>A
ENST00000356839.9:c.1581G>A
ENST00000542255.6:c.439G>A
ENST00000543245.6:c.1650G>A
ENST00000578319.5:n.76G>A
ENST00000578711.1:n.865G>A
ENST00000578809.5:n.153G>A
ENST00000579391.1:n.189G>A
ENST00000579425.5:n.697G>A
ENST00000579546.1:c.320G>A
ENST00000579894.5:n.368G>A
ENST00000582450.1:n.89G>A
ENST00000583074.5:n.202G>A
ENST00000583850.5:n.356G>A
ENST00000583858.5:c.512G>A
ENST00000585203.6:n.772G>A
NM_000018.3:c.1581G>A
NM_001033859.2:c.1515G>A
NM_001270447.1:c.1650G>A
NM_001270448.1:c.1353G>A
NM_001033859.3:c.1515G>A
NM_001270447.2:c.1650G>A
NM_001270448.2:c.1353G>A

Likely Benign

• Met criteria codes: BP7 BP4 PM2_Supporting

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specification: ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Evidence submitted by expert panel

ACADVL VCEP

The c.1581G>A variant in ACADVL is a synonymous variant which occurs in exon 16 (out of 20). The results from 2 in silico splicing predictors (SpliceAI, MutationTaster) support that this variant does not affect splicing. In addition, it occurs at a nucleotide that is not conserved as shown by the 100 vertebrate Basewise Conservation by PhyloP track in the UCSC genome browser (BP4, BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00050 in European (Non-Finnish) population, which is lower than the ClinGen ACADVL Expert Panel threshold (<0.001 (0.1%)) for PM2_Supporting; however, this is not considered conflicting evidence with BP4 and BP7. In summary, this variant meets the criteria to be classified as likely 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: PM2, BP4, BP7 (ACADVL VCEP specifications version 1; approved November 9, 2021).

Met criteria codes

• BP7: The c.1581G>A p.(Pro527=) variant is a synonymous (silent) variant that is not predicted by (SpliceAI, MaxEntScn, NNSplice) to impact splicing (splice AI <0.2).
• BP4: The results from 2 in silico splicing predictors (SpliceAI, MutationTaster) support that this variant does not affect splicing. The position is not conserved (phyloP = -1.933 is less than -1.04)
• PM2_Supporting: The highest population minor allele frequency in gnomAD v2.1.1 is 0.00050 in European (Non-Finnish) population, which is lower than the ClinGen ACADVL Expert Panel threshold (<0.001 (0.1%)) for PM2_Supporting, meeting this criterion (PM2_Supporting).