rs12547845
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_177924.5(ASAH1):c.126-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,467,130 control chromosomes in the GnomAD database, including 172,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.43 ( 14933 hom., cov: 31)
Exomes 𝑓: 0.48 ( 157657 hom. )
Consequence
ASAH1
NM_177924.5 intron
NM_177924.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.776
Genes affected
ASAH1 (HGNC:735): (N-acylsphingosine amidohydrolase 1) This gene encodes a member of the acid ceramidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. Processing of this preproprotein generates alpha and beta subunits that heterodimerize to form the mature lysosomal enzyme, which catalyzes the degradation of ceramide into sphingosine and free fatty acid. This enzyme is overexpressed in multiple human cancers and may play a role in cancer progression. Mutations in this gene are associated with the lysosomal storage disorder, Farber lipogranulomatosis, and a neuromuscular disorder, spinal muscular atrophy with progressive myoclonic epilepsy. [provided by RefSeq, Oct 2015]
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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 8-18071411-T-C is Benign according to our data. Variant chr8-18071411-T-C is described in ClinVar as [Benign]. Clinvar id is 259277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASAH1 | NM_177924.5 | c.126-21A>G | intron_variant | ENST00000637790.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASAH1 | ENST00000637790.2 | c.126-21A>G | intron_variant | 1 | NM_177924.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.430 AC: 65227AN: 151782Hom.: 14917 Cov.: 31
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GnomAD3 exomes AF: 0.494 AC: 104458AN: 211334Hom.: 26750 AF XY: 0.497 AC XY: 56088AN XY: 112832
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GnomAD4 exome AF: 0.485 AC: 637842AN: 1315230Hom.: 157657 Cov.: 20 AF XY: 0.488 AC XY: 320838AN XY: 657758
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GnomAD4 genome ? AF: 0.430 AC: 65282AN: 151900Hom.: 14933 Cov.: 31 AF XY: 0.431 AC XY: 31960AN XY: 74236
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | 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. - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 22, 2015 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Spinal muscular atrophy-progressive myoclonic epilepsy syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Farber lipogranulomatosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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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