8-18056822-ACTTC-A

Position:

• chr8-18056822-ACTTC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_177924.5(ASAH1):​c.*708_*711delGAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,974 control chromosomes in the GnomAD database, including 3,492 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3492 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASAH1 NM_177924.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.98

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 -10 ACMG points.

• BP6: Variant 8-18056822-ACTTC-A is Benign according to our data. Variant chr8-18056822-ACTTC-A is described in ClinVar as [Benign]. Clinvar id is 362357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1	NM_177924.5	c.*708_*711delGAAG		3_prime_UTR_variant	14/14	ENST00000637790.2	NP_808592.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAH1	ENST00000637790	c.*708_*711delGAAG		3_prime_UTR_variant	14/14	1	NM_177924.5	ENSP00000490272.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25927 AN: 151856 Hom.: 3484 Cov.: 30

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0800

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.149

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.171 AC: 25968 AN: 151974 Hom.: 3492 Cov.: 30 AF XY: 0.177 AC XY: 13122 AN XY: 74300

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0800

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.147

Alfa AF: 0.109 Hom.: 229

Bravo AF: 0.186

Asia WGS AF: 0.267 AC: 927 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Farber lipogranulomatosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs35838806; hg19: chr8-17914331;