dbSNP rs35838806: ASAH1:c.*708_*711delGAAG (chr8-18056822-ACTTC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_177924.5(ASAH1):c.*708_*711delGAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,974 control chromosomes in the GnomAD database, including 3,492 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 3492 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ASAH1
NM_177924.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.98

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 8-18056822-ACTTC-A is Benign according to our data. Variant chr8-18056822-ACTTC-A is described in ClinVar as [Benign]. Clinvar id is 362357.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAH1	NM_177924.5 link	c.708_711delGAAG		3_prime_UTR_variant	Exon 14 of 14	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.708_711delGAAG		3_prime_UTR_variant	Exon 14 of 14	1	NM_177924.5	ENSP00000490272.1		Q13510-1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25927

AN:

151856

Hom.:

3484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.0800

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0531

Gnomad OTH

AF:

0.149

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.171

AC:

25968

AN:

151974

Hom.:

3492

Cov.:

AF XY:

0.177

AC XY:

13122

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.345

AC:

14262

AN:

41352

American (AMR)

AF:

0.235

AC:

3580

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

433

AN:

3468

East Asian (EAS)

AF:

0.340

AC:

1756

AN:

5166

South Asian (SAS)

AF:

0.236

AC:

1136

AN:

4822

European-Finnish (FIN)

AF:

0.0800

AC:

848

AN:

10602

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0530

AC:

3608

AN:

68012

Other (OTH)

AF:

0.147

AC:

311

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

945

1890

2834

3779

4724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.109

Hom.:

229

Bravo

AF:

0.186

Asia WGS

AF:

0.267

AC:

927

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Farber lipogranulomatosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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rs35838806

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over