11-134253842-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014384.3(ACAD8):c.109+133G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 974,908 control chromosomes in the GnomAD database, including 652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.037 ( 124 hom., cov: 32)
Exomes 𝑓: 0.032 ( 528 hom. )
Consequence
ACAD8
NM_014384.3 intron
NM_014384.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.203
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 11-134253842-G-C is Benign according to our data. Variant chr11-134253842-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 673122.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.037 (5551/150156) while in subpopulation AFR AF= 0.0428 (1748/40800). AF 95% confidence interval is 0.0412. There are 124 homozygotes in gnomad4. There are 2653 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 124 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAD8 | NM_014384.3 | c.109+133G>C | intron_variant | ENST00000281182.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAD8 | ENST00000281182.9 | c.109+133G>C | intron_variant | 1 | NM_014384.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0370 AC: 5548AN: 150046Hom.: 124 Cov.: 32
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GnomAD4 exome AF: 0.0323 AC: 26599AN: 824752Hom.: 528 AF XY: 0.0317 AC XY: 13497AN XY: 425900
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GnomAD4 genome ? AF: 0.0370 AC: 5551AN: 150156Hom.: 124 Cov.: 32 AF XY: 0.0362 AC XY: 2653AN XY: 73314
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at