Variant 8-18084767-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000381733.9(ASAH1):c.35G>C(p.Arg12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,634 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 4 hom. )

Consequence

ASAH1
ENST00000381733.9 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: -1.51

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040474534).

BP6

Variant 8-18084767-C-G is Benign according to our data. Variant chr8-18084767-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 433108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-18084767-C-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASAH1	NM_004315.6 linkuse as main transcript	c.35G>C	p.Arg12Pro	missense_variant	1/14
ASAH1	NM_001127505.3 linkuse as main transcript	c.35G>C	p.Arg12Pro	missense_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASAH1-AS1	ENST00000665050.1 linkuse as main transcript	n.382C>G		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00133

AC:

333

AN:

249918

Hom.:

AF XY:

0.00133

AC XY:

179

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.000598

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000198

Gnomad FIN exome

AF:

0.00464

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00118

AC:

1721

AN:

1461318

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

922

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00468

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152316

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

118

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00170

Hom.:

Bravo

AF:

0.000752

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00142

AC:

172

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00143

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Childhood epilepsy with centrotemporal spikes

Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Bioinformatics Core, Luxembourg Center for Systems Biomedicine

Jan 01, 2017

CAADphred>15 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

ASAH1: BP4, BS2; ASAH1-AS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.2

DANN

Benign

0.97

DEOGEN2

Benign

0.0063

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

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.80

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.0040

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

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.060

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

REVEL

Benign

0.086

Sift

Pathogenic

0.0

D;.;.;D;.;.;.

Sift4G

Pathogenic

0.0

D;.;.;D;.;.;.

Polyphen

0.82

P;.;.;.;.;.;.

Vest4

0.35

MVP

0.42

MPC

0.0056

ClinPred

0.12

GERP RS

-2.1

gMVP

0.53

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