rs34859055

chr8-18071253-T-TATAchr8-18071253-T-TATC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_177924.5(ASAH1):c.216+46_216+47insTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14855 hom., cov: 0)
  • Exomes 𝑓: 0.45 (91896 hom.)
• Consequence: ASAH1 NM_177924.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.469

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 8-18071253-T-TATA is Benign according to our data. Variant chr8-18071253-T-TATA is described in ClinVar as [Likely_benign]. Clinvar id is 259279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASAH1	NM_177924.5	c.216+46_216+47insTAT		intron_variant		ENST00000637790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASAH1	ENST00000637790.2	c.216+46_216+47insTAT		intron_variant		1	NM_177924.5	P2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 64715 AN: 147284 Hom.: 14839 Cov.: 0

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.477

GnomAD3 exomes AF: 0.474 AC: 32721 AN: 68998 Hom.: 8294 AF XY: 0.483 AC XY: 18832 AN XY: 39012

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.288

Gnomad SAS exome AF: 0.529

Gnomad FIN exome AF: 0.405

Gnomad NFE exome AF: 0.482

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.454 AC: 388599 AN: 856834 Hom.: 91896 Cov.: 12 AF XY: 0.457 AC XY: 195960 AN XY: 428576

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.439 AC: 64769 AN: 147392 Hom.: 14855 Cov.: 0 AF XY: 0.441 AC XY: 31691 AN XY: 71904

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.474

Alfa AF: 0.194 Hom.: 444

Asia WGS AF: 0.413 AC: 1427 AN: 3456

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34859055; hg19: chr8-17928762;