Variant 8-18067340-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.304-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,179,346 control chromosomes in the GnomAD database, including 73,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 9758 hom., cov: 31)

Exomes 𝑓: 0.34 ( 63477 hom. )

Consequence

ASAH1
NM_177924.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.54

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=-0.82).

BP6

Variant 8-18067340-C-T is Benign according to our data. Variant chr8-18067340-C-T is described in ClinVar as [Benign]. Clinvar id is 259280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASAH1	NM_177924.5 linkuse as main transcript	c.304-42G>A		intron_variant		ENST00000637790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASAH1	ENST00000637790.2 linkuse as main transcript	c.304-42G>A		intron_variant		1	NM_177924.5	P2	Q13510-1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

53156

AN:

148660

Hom.:

9759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.336

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.345

AC:

37816

AN:

109580

Hom.:

6937

AF XY:

0.357

AC XY:

21290

AN XY:

59556

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.493

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.343

AC:

353756

AN:

1030668

Hom.:

63477

Cov.:

AF XY:

0.347

AC XY:

178433

AN XY:

514074

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.470

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.358

AC:

53158

AN:

148678

Hom.:

9758

Cov.:

AF XY:

0.361

AC XY:

26178

AN XY:

72484

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.444

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.521

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.343

Hom.:

1880

Bravo

AF:

0.365

Asia WGS

AF:

0.397

AC:

1366

AN:

3438

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	Aug 18, 2019	- -

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

-0.82

CADD

Benign

0.24

DANN

Benign

0.16

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