Variant 8-18084823-A-G 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_004315.6(ASAH1):c.-22T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,611,716 control chromosomes in the GnomAD database, including 1,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 115 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1295 hom. )

Consequence

ASAH1
NM_004315.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.919

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:):

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 (BayesDel_noAF=-0.79).

BP6

Variant 8-18084823-A-G is Benign according to our data. Variant chr8-18084823-A-G is described in ClinVar as [Benign]. Clinvar id is 558961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-18084823-A-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
ASAH1	NM_004315.6 linkuse as main transcript	c.-22T>C	5_prime_UTR_variant	1/14	NP_004306.3	Q13510-2Q53H01A8K0B6
ASAH1	NM_001127505.3 linkuse as main transcript	c.-22T>C	5_prime_UTR_variant	1/14	NP_001120977.1	Q13510-3Q53H01A8K0B6
ASAH1-AS1	NR_125429.1 linkuse as main transcript	n.-45A>G	upstream_gene_variant
ASAH1-AS1	NR_125430.1 linkuse as main transcript	n.-45A>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
ASAH1	ENST00000381733.9 linkuse as main transcript	c.-22T>C	5_prime_UTR_variant	1/14	1	ENSP00000371152.4	Q13510-2
ASAH1	ENST00000314146.10 linkuse as main transcript	c.-22T>C	5_prime_UTR_variant	1/14	1	ENSP00000326970.10	Q13510-3
ASAH1	ENST00000637244.1 linkuse as main transcript	n.-22T>C	non_coding_transcript_exon_variant	1/14	1	ENSP00000490188.1	A0A1B0GUP1

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

4996

AN:

152072

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0241

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0537

Gnomad FIN

AF:

0.0481

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0409

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0384

AC:

9507

AN:

247676

Hom.:

231

AF XY:

0.0411

AC XY:

5507

AN XY:

134106

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0744

Gnomad EAS exome

AF:

0.000819

Gnomad SAS exome

AF:

0.0610

Gnomad FIN exome

AF:

0.0473

Gnomad NFE exome

AF:

0.0425

Gnomad OTH exome

AF:

0.0479

GnomAD4 exome

AF:

0.0389

AC:

56723

AN:

1459526

Hom.:

1295

Cov.:

AF XY:

0.0399

AC XY:

28986

AN XY:

725938

show subpopulations

Gnomad4 AFR exome

AF:

0.0143

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.0751

Gnomad4 EAS exome

AF:

0.000429

Gnomad4 SAS exome

AF:

0.0605

Gnomad4 FIN exome

AF:

0.0482

Gnomad4 NFE exome

AF:

0.0387

Gnomad4 OTH exome

AF:

0.0397

GnomAD4 genome

AF:

0.0328

AC:

4994

AN:

152190

Hom.:

115

Cov.:

AF XY:

0.0328

AC XY:

2441

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0241

Gnomad4 ASJ

AF:

0.0778

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0535

Gnomad4 FIN

AF:

0.0481

Gnomad4 NFE

AF:

0.0409

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0397

Hom.:

Bravo

AF:

0.0296

Asia WGS

AF:

0.0300

AC:

106

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 15, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.7

DANN

Benign

0.62

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