rs12155668

chr8-18067642-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177924.5(ASAH1):c.304-344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 157,942 control chromosomes in the GnomAD database, including 14,996 homozygotes. 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: 𝑓 0.42 (14396 hom., cov: 30)
  • Exomes 𝑓: 0.42 (600 hom.)
• Consequence: ASAH1 NM_177924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASAH1	NM_177924.5	c.304-344G>A		intron_variant		ENST00000637790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASAH1	ENST00000637790.2	c.304-344G>A		intron_variant		1	NM_177924.5	P2

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63714 AN: 151370 Hom.: 14379 Cov.: 30

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.421 AC: 2716 AN: 6450 Hom.: 600 Cov.: 0 AF XY: 0.427 AC XY: 2058 AN XY: 4822

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.421 AC: 63772 AN: 151492 Hom.: 14396 Cov.: 30 AF XY: 0.421 AC XY: 31161 AN XY: 74006

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.453

Alfa AF: 0.487 Hom.: 15159

Bravo AF: 0.426

Asia WGS AF: 0.410 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	6.7
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12155668; hg19: chr8-17925151;