8-18075949-C-T

Position:

• chr8-18075949-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.79-362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 336,136 control chromosomes in the GnomAD database, including 55,965 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 0.57 (25424 hom., cov: 32)
  • Exomes 𝑓: 0.57 (30541 hom.)
• Consequence: ASAH1 NM_177924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1	NM_177924.5	c.79-362G>A		intron_variant		ENST00000637790.2	NP_808592.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAH1	ENST00000637790.2	c.79-362G>A		intron_variant		1	NM_177924.5	ENSP00000490272.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87098 AN: 151888 Hom.: 25423 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.534

GnomAD4 exome AF: 0.567 AC: 104420 AN: 184130 Hom.: 30541 Cov.: 0 AF XY: 0.557 AC XY: 56477 AN XY: 101468

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.656

Gnomad4 NFE exome AF: 0.613

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.573 AC: 87132 AN: 152006 Hom.: 25424 Cov.: 32 AF XY: 0.568 AC XY: 42228 AN XY: 74298

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.538

Alfa AF: 0.592 Hom.: 15592

Bravo AF: 0.557

Asia WGS AF: 0.423 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.17

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: rs10105871; hg19: chr8-17933458; COSMIC: COSV50505962; COSMIC: COSV50505962;