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.693T>A (p.Ser231=)

CA289257

136261 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5c47d0ce-9b49-4acb-8c42-f4302f28a649

HGVS expressions

NM_000018.4:c.693T>A

NM_000018.4(ACADVL):c.693T>A (p.Ser231=)

NC_000017.11:g.7222022T>A

CM000679.2:g.7222022T>A

NC_000017.10:g.7125341T>A

CM000679.1:g.7125341T>A

NC_000017.9:g.7066065T>A

NG_007975.1:g.7189T>A

NG_008391.2:g.3029A>T

ENST00000356839.10:c.693T>A

ENST00000322910.9:c.*648T>A

ENST00000350303.9:c.627T>A

ENST00000356839.9:c.693T>A

ENST00000543245.6:c.762T>A

ENST00000577191.5:n.770T>A

ENST00000577857.5:n.509T>A

ENST00000579286.5:n.874T>A

ENST00000580365.1:n.424T>A

ENST00000581378.5:c.411T>A

ENST00000582379.1:n.77T>A

ENST00000583760.1:n.475T>A

NM_000018.3:c.693T>A

NM_001033859.2:c.627T>A

NM_001270447.1:c.762T>A

NM_001270448.1:c.465T>A

NM_001033859.3:c.627T>A

NM_001270447.2:c.762T>A

NM_001270448.2:c.465T>A

Benign

BA1 BP7 BP4

PVS1 PM4 BP3

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL):c.693T>A (p.Ser231=) variant is a synonymous (silent) variant that is not predicted by SpliceAI and NNSplice to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by PhyloP and PhastCons (BP4, BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.2061 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). 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 (ACADVL VCEP specifications version 1; approved November 9, 2021).

BA1

BA1 is met; highest continental population MAF = 2.061% (AFR) >= 0.7% max pop MAF established by ACADVL working group

BP7

BP4 is met; variant is predicted to result in a synonymous substitution; 2 of 3 agree with no predicted abnormal splicing; SpliceAI predicts no impact on splicing (delta score = 0); potential loss of cryptic 3' acceptor 11 nucleotides downstream (MaxEntScn >15% reduction (WT=4.5, MUT=0), NNSplice no prediction of cryptic site); potential gain of 3' splice acceptor at variant position (MaxEntScn (WT=0, MUT=2.08)

BP4

Splice AI, NNSplice predict no change to splicing.

PVS1

PVS1 is not met; variant is predicted to result in a synonymous substitution

PM4

PM4 is not met; variant is predicted to result in a synonymous substitution

BP3

BP3 is not met; variant is predicted to result in a synonymous substitution

Approved on: 2024-03-26

Published on: 2024-03-26

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