chr8-18084559-C-T

Variant names:

• chr8-18084559-C-T
• rs571527083
• ENST00000381733.9:c.126+117G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004315.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH1	NM_004315.6		c.126+117G>A		intron	N/A	NP_004306.3
	ASAH1	NM_001127505.3		c.126+117G>A		intron	N/A	NP_001120977.1	Q13510-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH1	ENST00000381733.9	TSL:1	c.126+117G>A		intron	N/A	ENSP00000371152.4	Q13510-2
	ASAH1	ENST00000314146.10	TSL:1	c.126+117G>A		intron	N/A	ENSP00000326970.10	Q13510-3
	ASAH1	ENST00000637244.1	TSL:1	n.*18G>A		non_coding_transcript_exon	Exon 1 of 14	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

African (AFR) AF: 0.00 AC: 0 AN: 31850

American (AMR) AF: 0.00 AC: 0 AN: 36430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24836

East Asian (EAS) AF: 0.00 AC: 0 AN: 37228

South Asian (SAS) AF: 0.00 AC: 0 AN: 79134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4592

European-Non Finnish (NFE) AF: 9.47e-7 AC: 1 AN: 1056242

Other (OTH) AF: 0.00 AC: 0 AN: 57146

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.88
PhyloP100		-0.47
PromoterAI		0.037	Neutral

Splicing

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

Other links and lift over

dbSNP: rs571527083; hg19: chr8-17942068;