rs117035302
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000048.4(ASL):c.718+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,614,052 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.017 ( 62 hom., cov: 32)
Exomes 𝑓: 0.011 ( 446 hom. )
Consequence
ASL
NM_000048.4 intron
NM_000048.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.329
Genes affected
ASL (HGNC:746): (argininosuccinate lyase) This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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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=-0.83).
BP6
?
Variant 7-66087805-A-T is Benign according to our data. Variant chr7-66087805-A-T is described in ClinVar as [Benign]. Clinvar id is 254742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-66087805-A-T is described in Lovd as [Benign]. Variant chr7-66087805-A-T is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASL | NM_000048.4 | c.718+14A>T | intron_variant | ENST00000304874.14 | |||
ASL | NM_001024943.2 | c.718+14A>T | intron_variant | ||||
ASL | NM_001024944.2 | c.718+14A>T | intron_variant | ||||
ASL | NM_001024946.2 | c.640+14A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASL | ENST00000304874.14 | c.718+14A>T | intron_variant | 1 | NM_000048.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0165 AC: 2515AN: 152132Hom.: 61 Cov.: 32
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GnomAD3 exomes AF: 0.0226 AC: 5676AN: 251186Hom.: 142 AF XY: 0.0205 AC XY: 2785AN XY: 135834
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GnomAD4 exome AF: 0.0108 AC: 15726AN: 1461802Hom.: 446 Cov.: 32 AF XY: 0.0105 AC XY: 7614AN XY: 727198
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GnomAD4 genome ? AF: 0.0166 AC: 2527AN: 152250Hom.: 62 Cov.: 32 AF XY: 0.0196 AC XY: 1458AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 17, 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. - |
Argininosuccinate lyase deficiency Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at