rs1056471
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000183.3(HADHB):c.*136G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 763,492 control chromosomes in the GnomAD database, including 293,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.87 ( 59285 hom., cov: 33)
Exomes 𝑓: 0.85 ( 233964 hom. )
Consequence
HADHB
NM_000183.3 3_prime_UTR
NM_000183.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.868
Genes affected
HADHB (HGNC:4803): (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta) This gene encodes the beta subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the beta subunit catalyzing the 3-ketoacyl-CoA thiolase activity. The encoded protein can also bind RNA and decreases the stability of some mRNAs. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. Mutations in this gene result in trifunctional protein deficiency. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
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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=-0.7).
BP6
?
Variant 2-26290089-G-C is Benign according to our data. Variant chr2-26290089-G-C is described in ClinVar as [Benign]. Clinvar id is 335410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HADHB | NM_000183.3 | c.*136G>C | 3_prime_UTR_variant | 16/16 | ENST00000317799.10 | ||
HADHB | NM_001281512.2 | c.*136G>C | 3_prime_UTR_variant | 15/15 | |||
HADHB | NM_001281513.2 | c.*136G>C | 3_prime_UTR_variant | 17/17 | |||
HADHB | XM_011532803.2 | c.*136G>C | 3_prime_UTR_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HADHB | ENST00000317799.10 | c.*136G>C | 3_prime_UTR_variant | 16/16 | 1 | NM_000183.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.870 AC: 132313AN: 152162Hom.: 59230 Cov.: 33
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GnomAD4 exome AF: 0.853 AC: 521537AN: 611212Hom.: 233964 Cov.: 6 AF XY: 0.859 AC XY: 286689AN XY: 333710
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GnomAD4 genome ? AF: 0.870 AC: 132427AN: 152280Hom.: 59285 Cov.: 33 AF XY: 0.862 AC XY: 64218AN XY: 74470
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Mitochondrial trifunctional protein deficiency Benign:1
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
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