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]

Variant: NM_000018.4(ACADVL):c.1183-7A>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA8338033

567061 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 77ec6c61-af04-4683-8651-309503839c97

Approved on: 2022-09-22

Published on: 2022-09-22

HGVS expressions

NM_000018.4:c.1183-7A>G

NM_000018.4(ACADVL):c.1183-7A>G

NC_000017.11:g.7223637A>G

CM000679.2:g.7223637A>G

NC_000017.10:g.7126956A>G

CM000679.1:g.7126956A>G

NC_000017.9:g.7067680A>G

NG_007975.1:g.8804A>G

NG_008391.2:g.1414T>C

NG_033038.1:g.15908T>C

ENST00000356839.10:c.1183-7A>G

ENST00000322910.9:c.*1138-7A>G

ENST00000350303.9:c.1117-7A>G

ENST00000356839.9:c.1183-7A>G

ENST00000542255.6:n.41-7A>G

ENST00000543245.6:c.1252-7A>G

ENST00000578579.2:n.347A>G

ENST00000578711.1:n.133A>G

ENST00000578824.5:n.599-7A>G

ENST00000579425.5:n.207-7A>G

ENST00000579546.1:n.20-7A>G

ENST00000583858.5:n.212-7A>G

ENST00000585203.6:n.391-7A>G

NM_000018.3:c.1183-7A>G

NM_001033859.2:c.1117-7A>G

NM_001270447.1:c.1252-7A>G

NM_001270448.1:c.955-7A>G

NM_001033859.3:c.1117-7A>G

NM_001270447.2:c.1252-7A>G

NM_001270448.2:c.955-7A>G

Uncertain Significance

PM2_Supporting PM3_Supporting PP3 PP4

PM5 PM1 BP7 BP1 BP2 PS1

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1183-7A>G variant in ACADVL occurs within splice acceptor site of intron 11. The results from two in silico splicing predictors (MaxEntScn and Human Splicing Finder) indicate that this variant may affect splicing by disrupting the acceptor splice site of intron 11 of 20 in ACADVL (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). At least one patient with this variant displayed C14:1-carnitine level at 15.5 micromolar, which is highly specific for VLCAD deficiency (PP4_Supporting, PMID: 31031081). Due to limited evidence, this variant is classified as a variant of uncertain significance for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM2_Supporting, and PP4_Supporting.

PM2_Supporting

PM2_Supporting is met; Absent in gnomAD, observed 1/121360 ExAC, absent 1K and absent ESP.

PM3_Supporting

Total points = 0.5; Authors mention that variant is found in trans with pathogenic c.1322G>A p.(G441D); unknown phasing (PMID:31031081).

PP3

PP3 is met; New splice site is predicted; this rule can be applied if the newly generated splice site is significantly stronger than the wild type site (>2% difference using Human Splicing Finder and >15% difference using MaxEntScn).

PP4

PP4 is met; Symptomatic case with C14:1-carnitine peak at 15.57 μmol/L; no enzyme measurement (PMID:31031081).

PM5

PM5 is not met; Variant is found at intron 12.

PM1

PM1 is not met; Variant is located at intron 12.

BP7

BP7 is not met; Variant is located at intron 12.

BP1

BP1 is not met; Variant is found at intron 12.

BP2

BP2 is not met; Variant has not been observed in cis with a pathogenic variant in ACADVL.

PS1

PS1 is not met; Variant is found at intron 12.

Curation History

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