rs2427746
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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.303+117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 705,090 control chromosomes in the GnomAD database, including 55,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.36 ( 11122 hom., cov: 32)
Exomes 𝑓: 0.39 ( 44706 hom. )
Consequence
ASAH1
NM_177924.5 intron
NM_177924.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.340
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=-0.86).
BP6
Variant 8-18069675-A-G is Benign according to our data. Variant chr8-18069675-A-G is described in ClinVar as [Benign]. Clinvar id is 678030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASAH1 | NM_177924.5 | c.303+117T>C | intron_variant | ENST00000637790.2 | NP_808592.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASAH1 | ENST00000637790.2 | c.303+117T>C | intron_variant | 1 | NM_177924.5 | ENSP00000490272.1 |
Frequencies
GnomAD3 genomes AF: 0.362 AC: 55057AN: 151976Hom.: 11104 Cov.: 32
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GnomAD4 exome AF: 0.394 AC: 217812AN: 552998Hom.: 44706 Cov.: 7 AF XY: 0.399 AC XY: 118201AN XY: 296586
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GnomAD4 genome AF: 0.362 AC: 55097AN: 152092Hom.: 11122 Cov.: 32 AF XY: 0.363 AC XY: 26945AN XY: 74330
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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. - |
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