chr15-40405780-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000651168.1(IVD):c.-39G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,599,770 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 25 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 17 hom. )
Consequence
IVD
ENST00000651168.1 5_prime_UTR
ENST00000651168.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.447
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 15-40405780-G-A is Benign according to our data. Variant chr15-40405780-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 315796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1529/152388) while in subpopulation AFR AF= 0.0345 (1436/41592). AF 95% confidence interval is 0.033. There are 25 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 25 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IVD | NM_002225.5 | upstream_gene_variant | ENST00000487418.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IVD | ENST00000487418.8 | upstream_gene_variant | 1 | NM_002225.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0100 AC: 1529AN: 152270Hom.: 26 Cov.: 33
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GnomAD3 exomes AF: 0.00280 AC: 687AN: 245478Hom.: 8 AF XY: 0.00231 AC XY: 308AN XY: 133322
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GnomAD4 exome AF: 0.00117 AC: 1700AN: 1447382Hom.: 17 Cov.: 31 AF XY: 0.00106 AC XY: 762AN XY: 717240
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GnomAD4 genome AF: 0.0100 AC: 1529AN: 152388Hom.: 25 Cov.: 33 AF XY: 0.0100 AC XY: 748AN XY: 74518
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Isovaleryl-CoA dehydrogenase deficiency Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 24, 2016 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at