20-3213247-A-C
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1
The NM_033453.4(ITPA):c.124+21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,972 control chromosomes in the GnomAD database, including 11,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).
Frequency
Genomes: 𝑓 0.096 ( 823 hom., cov: 32)
Exomes 𝑓: 0.12 ( 11012 hom. )
Consequence
ITPA
NM_033453.4 intron
NM_033453.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.323
Genes affected
ITPA (HGNC:6176): (inosine triphosphatase) This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 20-3213247-A-C is Benign according to our data. Variant chr20-3213247-A-C is described in ClinVar as [drug_response]. Clinvar id is 14747.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Benign=3, drug_response=1}.
BA1
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GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPA | NM_033453.4 | c.124+21A>C | intron_variant | ENST00000380113.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPA | ENST00000380113.8 | c.124+21A>C | intron_variant | 1 | NM_033453.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0960 AC: 14592AN: 152070Hom.: 822 Cov.: 32
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GnomAD3 exomes AF: 0.0873 AC: 21964AN: 251474Hom.: 1189 AF XY: 0.0866 AC XY: 11769AN XY: 135918
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GnomAD4 exome AF: 0.118 AC: 171805AN: 1461784Hom.: 11012 Cov.: 35 AF XY: 0.115 AC XY: 83336AN XY: 727202
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GnomAD4 genome ? AF: 0.0959 AC: 14593AN: 152188Hom.: 823 Cov.: 32 AF XY: 0.0912 AC XY: 6784AN XY: 74404
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ClinVar
Significance: drug response
Submissions summary: Benign:3Other:2
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Inosine triphosphatase deficiency Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Affects, no assertion criteria provided | literature only | OMIM | Oct 01, 2002 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | This variant is associated with the following publications: (PMID: 19579612, 12384777, 20547162, 22613675, 17113761, 20173735, 22939045) - |
Developmental and epileptic encephalopathy, 35 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
peginterferon alfa-2b and ribavirin response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Mar 24, 2021 | PharmGKB Level of Evidence 2B: Variants in Level 2B clinical annotations are not in PharmGKB’s Tier 1 VIPs. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2B clinical annotations must be supported by at least two independent publications. Drug-variant association: Toxicity |
Computational scores
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Name
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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