8-18060379-C-T

Position:

• chr8-18060379-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.786-676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,348 control chromosomes in the GnomAD database, including 12,954 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 0.40 (12919 hom., cov: 32)
  • Exomes 𝑓: 0.38 (35 hom.)
• Consequence: ASAH1 NM_177924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1	NM_177924.5	c.786-676G>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.786-676G>A		intron_variant		1	NM_177924.5	ENSP00000490272.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60892 AN: 151838 Hom.: 12903 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.375 AC: 147 AN: 392 Hom.: 35 Cov.: 0 AF XY: 0.369 AC XY: 87 AN XY: 236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.401 AC: 60958 AN: 151956 Hom.: 12919 Cov.: 32 AF XY: 0.409 AC XY: 30374 AN XY: 74282

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.406

Alfa AF: 0.369 Hom.: 5446

Bravo AF: 0.414

Asia WGS AF: 0.609 AC: 2118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.81
DANN	Benign	0.44

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: rs10112857; hg19: chr8-17917888;