chr11-134256539-T-C
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_014384.3(ACAD8):c.110-9T>C variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000049 in 1,612,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000046 ( 0 hom. )
Consequence
ACAD8
NM_014384.3 splice_polypyrimidine_tract, intron
NM_014384.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.8054
2
Clinical Significance
Conservation
PhyloP100: 3.69
Genes affected
ACAD8 (HGNC:87): (acyl-CoA dehydrogenase family member 8) This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. Defects in this gene are the cause of isobutyryl-CoA dehydrogenase deficiency.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 11-134256539-T-C is Benign according to our data. Variant chr11-134256539-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 303671.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| ACAD8 | NM_014384.3 | c.110-9T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000281182.9 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACAD8 | ENST00000281182.9 | c.110-9T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014384.3 | P1 |
Frequencies
GnomAD3 genomes 0.0000788 AC: 12AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251400Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135882
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GnomAD4 exome AF: 0.0000459 AC: 67AN: 1459800Hom.: 0 Cov.: 31 AF XY: 0.0000441 AC XY: 32AN XY: 726328
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GnomAD4 genome 0.0000788 AC: 12AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74376
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Deficiency of isobutyryl-CoA dehydrogenase Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at