chr15-40405792-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The ENST00000651168.1(IVD):c.-27C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,604,858 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
IVD
ENST00000651168.1 5_prime_UTR
ENST00000651168.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.33
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 -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 15-40405792-C-T is Benign according to our data. Variant chr15-40405792-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 507985.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000125 (182/1452470) while in subpopulation EAS AF= 0.00449 (177/39458). AF 95% confidence interval is 0.00395. There are 1 homozygotes in gnomad4_exome. There are 91 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
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: 0.0000460 AC: 7AN: 152270Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000564 AC: 14AN: 248160Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134690
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GnomAD4 exome AF: 0.000125 AC: 182AN: 1452470Hom.: 1 Cov.: 32 AF XY: 0.000126 AC XY: 91AN XY: 720648
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GnomAD4 genome AF: 0.0000459 AC: 7AN: 152388Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74518
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2017 | 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at