8-18084559-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004315.6(ASAH1):​c.126+117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,374,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ASAH1
NM_004315.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.465
Variant links:
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]
ASAH1-AS1 (HGNC:55603): (ASAH1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASAH1NM_004315.6 linkc.126+117G>A intron_variant Intron 1 of 13 NP_004306.3 Q13510-2Q53H01A8K0B6
ASAH1NM_001127505.3 linkc.126+117G>A intron_variant Intron 1 of 13 NP_001120977.1 Q13510-3Q53H01A8K0B6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASAH1ENST00000381733.9 linkc.126+117G>A intron_variant Intron 1 of 13 1 ENSP00000371152.4 Q13510-2
ASAH1ENST00000314146.10 linkc.126+117G>A intron_variant Intron 1 of 13 1 ENSP00000326970.10 Q13510-3
ASAH1ENST00000637244.1 linkn.*18G>A non_coding_transcript_exon_variant Exon 1 of 14 1 ENSP00000490188.1 A0A1B0GUP1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.28e-7
AC:
1
AN:
1374274
Hom.:
0
Cov.:
22
AF XY:
0.00000147
AC XY:
1
AN XY:
680250
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.47e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
4.6
DANN
Benign
0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-17942068; API