8-18084695-C-T

Variant names:

Variant summary

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

The NM_004315.6(ASAH1):c.107G>A(p.Ser36Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 1,613,174 control chromosomes in the GnomAD database, including 2,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 600 hom., cov: 33)

Exomes 𝑓: 0.050 ( 2262 hom. )

Consequence

ASAH1
NM_004315.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.139

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-AS1 (HGNC:55603): (ASAH1 antisense RNA 1)

ASAH1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017465055).

BP6

Variant 8-18084695-C-T is Benign according to our data. Variant chr8-18084695-C-T is described in ClinVar as [Benign]. Clinvar id is 558960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-18084695-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ASAH1	NM_004315.6 link	c.107G>A	p.Ser36Asn	missense_variant	Exon 1 of 14	NP_004306.3	Q13510-2Q53H01A8K0B6
ASAH1	NM_001127505.3 link	c.107G>A	p.Ser36Asn	missense_variant	Exon 1 of 14	NP_001120977.1	Q13510-3Q53H01A8K0B6
ASAH1-AS1	NR_125429.1 link	n.-173C>T		upstream_gene_variant
ASAH1-AS1	NR_125430.1 link	n.-173C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ASAH1	ENST00000381733.9 link	c.107G>A	p.Ser36Asn	missense_variant	Exon 1 of 14	1	ENSP00000371152.4	Q13510-2
ASAH1	ENST00000314146.10 link	c.107G>A	p.Ser36Asn	missense_variant	Exon 1 of 14	1	ENSP00000326970.10	Q13510-3
ASAH1	ENST00000637244.1 link	n.107G>A		non_coding_transcript_exon_variant	Exon 1 of 14	1	ENSP00000490188.1	A0A1B0GUP1

Frequencies

GnomAD3 genomes

AF:

0.0743

AC:

11282

AN:

151790

Hom.:

592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.0616

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0492

Gnomad OTH

AF:

0.0583

GnomAD3 exomes

AF:

0.0493

AC:

12266

AN:

248932

Hom.:

428

AF XY:

0.0481

AC XY:

6478

AN XY:

134620

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.0508

Gnomad SAS exome

AF:

0.0595

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.0481

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0504

AC:

73600

AN:

1461268

Hom.:

2262

Cov.:

AF XY:

0.0505

AC XY:

36716

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.0211

Gnomad4 ASJ exome

AF:

0.0240

Gnomad4 EAS exome

AF:

0.0747

Gnomad4 SAS exome

AF:

0.0594

Gnomad4 FIN exome

AF:

0.0343

Gnomad4 NFE exome

AF:

0.0484

Gnomad4 OTH exome

AF:

0.0509

GnomAD4 genome

AF:

0.0745

AC:

11322

AN:

151906

Hom.:

600

Cov.:

AF XY:

0.0729

AC XY:

5413

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.0377

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.0526

Gnomad4 SAS

AF:

0.0617

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.0492

Gnomad4 OTH

AF:

0.0572

Alfa

AF:

0.0509

Hom.:

446

Bravo

AF:

0.0770

TwinsUK

AF:

0.0415

AC:

154

ALSPAC

AF:

0.0446

AC:

172

ESP6500AA

AF:

0.145

AC:

640

ESP6500EA

AF:

0.0484

AC:

416

ExAC

AF:

0.0538

AC:

6535

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

EpiCase

AF:

0.0430

EpiControl

AF:

0.0415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 26, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.1

DANN

Benign

0.87

DEOGEN2

Benign

0.018

.;T;.;.;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.74

T;T;T;T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.97

N;.;.;N;.;.;.

REVEL

Benign

0.099

Sift

Benign

0.45

T;.;.;T;.;.;.

Sift4G

Benign

0.46

T;.;.;T;.;.;.

Polyphen

0.0070

B;.;.;.;.;.;.

Vest4

0.040

MPC

0.0033

ClinPred

0.0055

GERP RS

0.22

gMVP

0.30

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