8-18084512-T-C

Position:

• chr8-18084512-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004315.6(ASAH1):​c.126+164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,359,430 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (106 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (87 hom.)
• Consequence: ASAH1 NM_004315.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-18084512-T-C is Benign according to our data. Variant chr8-18084512-T-C is described in ClinVar as [Benign]. Clinvar id is 1293692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1	NM_004315.6	c.126+164A>G		intron_variant			NP_004306.3
ASAH1	NM_001127505.3	c.126+164A>G		intron_variant			NP_001120977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAH1	ENST00000381733.9	c.126+164A>G		intron_variant		1		ENSP00000371152.4
ASAH1	ENST00000314146.10	c.126+164A>G		intron_variant		1		ENSP00000326970.10
ASAH1	ENST00000637244.1	n.*65A>G		non_coding_transcript_exon_variant	1/14	1		ENSP00000490188.1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3162 AN: 152026 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00221 AC: 2673 AN: 1207286 Hom.: 87 Cov.: 16 AF XY: 0.00195 AC XY: 1169 AN XY: 599052

Gnomad4 AFR exome AF: 0.0730

Gnomad4 AMR exome AF: 0.00439

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000846

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000239

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome AF: 0.0209 AC: 3177 AN: 152144 Hom.: 106 Cov.: 33 AF XY: 0.0200 AC XY: 1485 AN XY: 74358

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.00837

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0133 Hom.: 10

Bravo AF: 0.0232

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112230670; hg19: chr8-17942021;