chr15-40405740-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000651168.1(IVD):c.-79C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,553,876 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0061 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 20 hom. )
Consequence
IVD
ENST00000651168.1 5_prime_UTR
ENST00000651168.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.135
Genes affected
IVD (HGNC:6186): (isovaleryl-CoA dehydrogenase) Isovaleryl-CoA dehydrogenase (IVD) is a mitochondrial matrix enzyme that catalyzes the third step in leucine catabolism. The genetic deficiency of IVD results in an accumulation of isovaleric acid, which is toxic to the central nervous system and leads to isovaleric acidemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]
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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=-0.79).
BP6
?
Variant 15-40405740-C-G is Benign according to our data. Variant chr15-40405740-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 315795.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00608 (926/152348) while in subpopulation AFR AF= 0.0187 (779/41578). AF 95% confidence interval is 0.0176. There are 9 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IVD | ENST00000650656.1 | c.-79C>G | 5_prime_UTR_variant | 1/11 | |||||
IVD | ENST00000651168.1 | c.-79C>G | 5_prime_UTR_variant | 1/12 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00608 AC: 926AN: 152230Hom.: 9 Cov.: 32
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GnomAD4 exome AF: 0.00129 AC: 1814AN: 1401528Hom.: 20 AF XY: 0.00153 AC XY: 1053AN XY: 689334
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GnomAD4 genome ? AF: 0.00608 AC: 926AN: 152348Hom.: 9 Cov.: 32 AF XY: 0.00636 AC XY: 474AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Isovaleryl-CoA dehydrogenase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at