chr8-18079855-C-T

Position:

• chr8-18079855-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.78+4126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,064 control chromosomes in the GnomAD database, including 18,651 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 0.49 (18651 hom., cov: 33)
• Consequence: ASAH1 NM_177924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1	NM_177924.5	c.78+4126G>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.78+4126G>A		intron_variant		1	NM_177924.5	ENSP00000490272	P2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74441 AN: 151946 Hom.: 18639 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.490 AC: 74492 AN: 152064 Hom.: 18651 Cov.: 33 AF XY: 0.486 AC XY: 36140 AN XY: 74326

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.481

Alfa AF: 0.520 Hom.: 35675

Bravo AF: 0.472

Asia WGS AF: 0.520 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.37

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: rs7825389; hg19: chr8-17937364;