Variant 8-18075637-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_177924.5(ASAH1):c.79-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,557,112 control chromosomes in the GnomAD database, including 6,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 881 hom., cov: 32)

Exomes 𝑓: 0.087 ( 6093 hom. )

Consequence

ASAH1
NM_177924.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.77

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 8-18075637-C-T is Benign according to our data. Variant chr8-18075637-C-T is described in ClinVar as [Benign]. Clinvar id is 259276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1	NM_177924.5 linkuse as main transcript	c.79-50G>A		intron_variant		ENST00000637790.2	NP_808592.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAH1	ENST00000637790.2 linkuse as main transcript	c.79-50G>A		intron_variant		1	NM_177924.5	ENSP00000490272	P2	Q13510-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15573

AN:

152038

Hom.:

881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0557

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0962

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0830

Gnomad OTH

AF:

0.0926

GnomAD3 exomes

AF:

0.106

AC:

26586

AN:

250192

Hom.:

1619

AF XY:

0.107

AC XY:

14409

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.0572

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.0941

Gnomad NFE exome

AF:

0.0837

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0871

AC:

122406

AN:

1404956

Hom.:

6093

Cov.:

AF XY:

0.0889

AC XY:

62459

AN XY:

702638

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.0534

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0915

Gnomad4 NFE exome

AF:

0.0778

Gnomad4 OTH exome

AF:

0.0920

GnomAD4 genome

AF:

0.102

AC:

15589

AN:

152156

Hom.:

881

Cov.:

AF XY:

0.103

AC XY:

7688

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.0554

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0962

Gnomad4 NFE

AF:

0.0830

Gnomad4 OTH

AF:

0.0921

Alfa

AF:

0.0685

Hom.:

149

Bravo

AF:

0.106

Asia WGS

AF:

0.0660

AC:

232

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Spinal muscular atrophy-progressive myoclonic epilepsy syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Farber lipogranulomatosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0040

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over