Variant 8-18071253-T-TATA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_177924.5(ASAH1):c.216+46_216+47insTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14855 hom., cov: 0)

Exomes 𝑓: 0.45 ( 91896 hom. )

Consequence

ASAH1
NM_177924.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.469

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:

ASAH1 (HGNC:):

ASAH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-18071253-T-TATA is Benign according to our data. Variant chr8-18071253-T-TATA is described in ClinVar as [Likely_benign]. Clinvar id is 259279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 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.216+46_216+47insTAT		intron_variant		ENST00000637790.2	NP_808592.2	Q13510-1Q53H01A8K0B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAH1	ENST00000637790.2 linkuse as main transcript	c.216+46_216+47insTAT		intron_variant		1	NM_177924.5	ENSP00000490272.1		Q13510-1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

64715

AN:

147284

Hom.:

14839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.625

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.440

Gnomad MID

AF:

0.439

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.477

GnomAD3 exomes

AF:

0.474

AC:

32721

AN:

68998

Hom.:

8294

AF XY:

0.483

AC XY:

18832

AN XY:

39012

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.571

Gnomad ASJ exome

AF:

0.608

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.529

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.477

GnomAD4 exome

AF:

0.454

AC:

388599

AN:

856834

Hom.:

91896

Cov.:

AF XY:

0.457

AC XY:

195960

AN XY:

428576

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.563

Gnomad4 ASJ exome

AF:

0.590

Gnomad4 EAS exome

AF:

0.385

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.385

Gnomad4 NFE exome

AF:

0.457

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.439

AC:

64769

AN:

147392

Hom.:

14855

Cov.:

AF XY:

0.441

AC XY:

31691

AN XY:

71904

show subpopulations

Gnomad4 AFR

AF:

0.282

Gnomad4 AMR

AF:

0.537

Gnomad4 ASJ

AF:

0.625

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.534

Gnomad4 FIN

AF:

0.440

Gnomad4 NFE

AF:

0.497

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.194

Hom.:

444

Asia WGS

AF:

0.413

AC:

1427

AN:

3456

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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