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.1038G>A (p.Ala346=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA145601

21012 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 13e9aeca-373a-462d-91a4-ae936c164558

Approved on: 2022-03-08

Published on: 2022-03-08

HGVS expressions

NM_000018.4:c.1038G>A

NM_000018.4(ACADVL):c.1038G>A (p.Ala346=)

NC_000017.11:g.7222826G>A

CM000679.2:g.7222826G>A

NC_000017.10:g.7126145G>A

CM000679.1:g.7126145G>A

NC_000017.9:g.7066869G>A

NG_007975.1:g.7993G>A

NG_008391.2:g.2225C>T

ENST00000356839.10:c.1038G>A

ENST00000322910.9:c.*993G>A

ENST00000350303.9:c.972G>A

ENST00000356839.9:c.1038G>A

ENST00000543245.6:c.1107G>A

ENST00000578824.5:n.187G>A

ENST00000582379.1:n.422G>A

ENST00000583858.5:n.67G>A

NM_000018.3:c.1038G>A

NM_001033859.2:c.972G>A

NM_001270447.1:c.1107G>A

NM_001270448.1:c.810G>A

NM_001033859.3:c.972G>A

NM_001270447.2:c.1107G>A

NM_001270448.2:c.810G>A

Benign

BA1 BP7 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.1038G>A variant in ACADVL is a synonymous variant which occurs in exon 10. The highest population minor allele frequency in gnomAD v2.1.1 is 0.08089 in the African/African American 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 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). 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, BP7 (VCEP specifications v2.0, approved on 09/16/2021).

BA1

Allele frequency in African population 0.08089 in gnomAD

BP7

Scores for SpliceAI were all below 0.2 (0.00, 0.01, 0.01, 0.06). No change was seen when a 45 bp region centered on the variant was tested with NNSplice. The nucleotide is not conserved as judged by the 100 vertebrate Basewise Conservation by PhyloP track in the UCSC genome browser

BP4

SpliceAI and NNSplice both predict no change in splicing

Curation History

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