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]

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Variant: NM_000018.4(ACADVL):c.1077+15C>T

CA8337936

509396 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3aa27d71-829b-477c-aebd-37a6dbe94fe7

Approved on: 2022-09-23

Published on: 2022-09-23

HGVS expressions

NM_000018.4:c.1077+15C>T

NM_000018.4(ACADVL):c.1077+15C>T

NC_000017.11:g.7222880C>T

CM000679.2:g.7222880C>T

NC_000017.10:g.7126199C>T

CM000679.1:g.7126199C>T

NC_000017.9:g.7066923C>T

NG_007975.1:g.8047C>T

NG_008391.2:g.2171G>A

ENST00000356839.10:c.1077+15C>T

ENST00000322910.9:c.*1032+15C>T

ENST00000350303.9:c.1011+15C>T

ENST00000356839.9:c.1077+15C>T

ENST00000543245.6:c.1146+15C>T

ENST00000578824.5:n.241C>T

ENST00000582379.1:n.476C>T

ENST00000583858.5:n.106+15C>T

ENST00000585203.6:n.33C>T

NM_000018.3:c.1077+15C>T

NM_001033859.2:c.1011+15C>T

NM_001270447.1:c.1146+15C>T

NM_001270448.1:c.849+15C>T

NM_001033859.3:c.1011+15C>T

NM_001270447.2:c.1146+15C>T

NM_001270448.2:c.849+15C>T

Likely Benign

BS1 BP4

BP2 PP4

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1077+15 C>T variant in ACADVL is an intronic variant which falls downstream of the exon 10 3' splice site. The highest population minor allele frequency in gnomAD v2.1.1 is 0.003767 in the Ashkenazi Jewish population with two homozygotes, which is higher than the ClinGen ACADVL VCEP threshold (>0.0035) for BS1, and therefore meets this criterion (BS1). One individual with this variant did display elevated C14:1 levels on newborn screening, however no values were specified. This same individual was compound heterozygous for this variant and two other variants, though the lack of confirmation in trans disallows this evidence from meeting BP2 (PMID: 27246109; Variants: p.Lys187Glu, c.1678+23 C>T). The results from two in silico splicing predictors (NNSPLICE, SpliceAI) support that this variant does not affect splicing (BP4). In summary, this variant meets the criteria to be classified as likely benign for VLCAD deficiency in an autosomal recessive manner based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL VCEP: BS1; BP4. Pilot Specifications; Approved on 08/11/2020.

BS1

gnomAD Allele frequency of 0.00377 in Ashkenazi Jewish; 2 reported homozygotes

BP4

NNSplice and SpliceAI predict no change from this variant

BP2

Although there are three variants reported in a proband, the lack of in-trans or in-cis information does not provide enough evidence to meet this criteria

PP4

Proband NBS values are not specified

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