rs190975135
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004044.7(ATIC):c.380-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000985 in 1,613,696 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 9 hom. )
Consequence
ATIC
NM_004044.7 intron
NM_004044.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.13
Genes affected
ATIC (HGNC:794): (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase) This gene encodes a bifunctional protein that catalyzes the last two steps of the de novo purine biosynthetic pathway. The N-terminal domain has phosphoribosylaminoimidazolecarboxamide formyltransferase activity, and the C-terminal domain has IMP cyclohydrolase activity. A mutation in this gene results in AICA-ribosiduria. [provided by RefSeq, Sep 2009]
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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=-0.91).
BP6
?
Variant 2-215325969-G-A is Benign according to our data. Variant chr2-215325969-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445428.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 = 0.00511 (778/152246) while in subpopulation AFR AF= 0.0179 (743/41540). AF 95% confidence interval is 0.0168. There are 6 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATIC | NM_004044.7 | c.380-18G>A | intron_variant | ENST00000236959.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATIC | ENST00000236959.14 | c.380-18G>A | intron_variant | 1 | NM_004044.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00511 AC: 778AN: 152128Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00149 AC: 371AN: 249810Hom.: 2 AF XY: 0.00114 AC XY: 154AN XY: 135182
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GnomAD4 exome AF: 0.000556 AC: 812AN: 1461450Hom.: 9 Cov.: 34 AF XY: 0.000483 AC XY: 351AN XY: 727040
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GnomAD4 genome ? AF: 0.00511 AC: 778AN: 152246Hom.: 6 Cov.: 32 AF XY: 0.00505 AC XY: 376AN XY: 74438
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 04, 2017 | - - |
AICA-ribosiduria Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 11, 2022 | - - |
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