chr9-32425678-T-G
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002197.3(ACO1):c.1189-160T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,036 control chromosomes in the GnomAD database, including 12,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.40 ( 12745 hom., cov: 33)
Consequence
ACO1
NM_002197.3 intron
NM_002197.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.94
Genes affected
ACO1 (HGNC:117): (aconitase 1) The protein encoded by this gene is a bifunctional, cytosolic protein that functions as an essential enzyme in the TCA cycle and interacts with mRNA to control the levels of iron inside cells. When cellular iron levels are high, this protein binds to a 4Fe-4S cluster and functions as an aconitase. Aconitases are iron-sulfur proteins that function to catalyze the conversion of citrate to isocitrate. When cellular iron levels are low, the protein binds to iron-responsive elements (IREs), which are stem-loop structures found in the 5' UTR of ferritin mRNA, and in the 3' UTR of transferrin receptor mRNA. When the protein binds to IRE, it results in repression of translation of ferritin mRNA, and inhibition of degradation of the otherwise rapidly degraded transferrin receptor mRNA. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Alternative splicing results in multiple transcript variants [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACO1 | NM_002197.3 | c.1189-160T>G | intron_variant | ENST00000309951.8 | |||
ACO1 | NM_001278352.2 | c.1189-160T>G | intron_variant | ||||
ACO1 | NM_001362840.2 | c.1189-160T>G | intron_variant | ||||
ACO1 | XM_047423430.1 | c.1213-160T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACO1 | ENST00000309951.8 | c.1189-160T>G | intron_variant | 1 | NM_002197.3 | P1 | |||
ACO1 | ENST00000379923.5 | c.1189-160T>G | intron_variant | 5 | P1 | ||||
ACO1 | ENST00000541043.5 | c.1189-160T>G | intron_variant | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.400 AC: 60791AN: 151918Hom.: 12715 Cov.: 33
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GnomAD4 genome ? AF: 0.400 AC: 60869AN: 152036Hom.: 12745 Cov.: 33 AF XY: 0.399 AC XY: 29650AN XY: 74330
GnomAD4 genome
?
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1464
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3476
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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