rs12547845

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_177924.5(ASAH1):c.126-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,467,130 control chromosomes in the GnomAD database, including 172,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14933 hom., cov: 31)

Exomes 𝑓: 0.48 ( 157657 hom. )

Consequence

ASAH1
NM_177924.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.776

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

ASAH1-related sphingolipidosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Farber lipogranulomatosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
spinal muscular atrophy-progressive myoclonic epilepsy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P

ASAH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-18071411-T-C is Benign according to our data. Variant chr8-18071411-T-C is described in ClinVar as Benign. ClinVar VariationId is 259277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAH1	NM_177924.5 link	c.126-21A>G		intron_variant	Intron 2 of 13	ENST00000637790.2	NP_808592.2	Q13510-1Q53H01A8K0B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAH1	ENST00000637790.2 link	c.126-21A>G		intron_variant	Intron 2 of 13	1	NM_177924.5	ENSP00000490272.1		Q13510-1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65227

AN:

151782

Hom.:

14917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.465

GnomAD2 exomes

AF:

0.494

AC:

104458

AN:

211334

AF XY:

0.497

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.655

Gnomad ASJ exome

AF:

0.609

Gnomad EAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.412

Gnomad NFE exome

AF:

0.488

Gnomad OTH exome

AF:

0.502

GnomAD4 exome

AF:

0.485

AC:

637842

AN:

1315230

Hom.:

157657

Cov.:

AF XY:

0.488

AC XY:

320838

AN XY:

657758

show subpopulations

African (AFR)

AF:

0.266

AC:

8133

AN:

30530

American (AMR)

AF:

0.638

AC:

26560

AN:

41652

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

15122

AN:

24804

East Asian (EAS)

AF:

0.403

AC:

15511

AN:

38506

South Asian (SAS)

AF:

0.538

AC:

43216

AN:

80262

European-Finnish (FIN)

AF:

0.412

AC:

21151

AN:

51288

Middle Eastern (MID)

AF:

0.488

AC:

2477

AN:

5076

European-Non Finnish (NFE)

AF:

0.485

AC:

479286

AN:

987894

Other (OTH)

AF:

0.478

AC:

26386

AN:

55218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

13252

26504

39755

53007

66259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13658

27316

40974

54632

68290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.430

AC:

65282

AN:

151900

Hom.:

14933

Cov.:

AF XY:

0.431

AC XY:

31960

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.276

AC:

11440

AN:

41420

American (AMR)

AF:

0.529

AC:

8076

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2148

AN:

3472

East Asian (EAS)

AF:

0.382

AC:

1964

AN:

5146

South Asian (SAS)

AF:

0.525

AC:

2526

AN:

4816

European-Finnish (FIN)

AF:

0.420

AC:

4416

AN:

10526

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.487

AC:

33085

AN:

67934

Other (OTH)

AF:

0.461

AC:

975

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1765

3531

5296

7062

8827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.473

Hom.:

3373

Bravo

AF:

0.434

Asia WGS

AF:

0.418

AC:

1453

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spinal muscular atrophy-progressive myoclonic epilepsy syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Farber lipogranulomatosis

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.79

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over