chr8-18085214-CTTT-C

Variant names:

• chr8-18085214-CTTT-C
• rs34250229
• ENST00000517798.2:n.834_836delTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000521775.6(ASAH1-AS1):​n.809_811delTTT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 236,212 control chromosomes in the GnomAD database, including 615 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (368 hom., cov: 32)
  • Exomes 𝑓: 0.046 (247 hom.)
• Consequence: ASAH1-AS1 ENST00000521775.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.707

Genes affected

ASAH1-AS1 (HGNC:55603): (ASAH1 antisense RNA 1)

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 -10 ACMG points.

• BP6: Variant 8-18085214-CTTT-C is Benign according to our data. Variant chr8-18085214-CTTT-C is described in ClinVar as [Benign]. Clinvar id is 1225771.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASAH1-AS1	NR_125429.1	n.73-23_73-21delTTT		intron_variant	Intron 1 of 4
ASAH1-AS1	NR_125430.1	n.72+280_72+282delTTT		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAH1-AS1	ENST00000517798.2	n.834_836delTTT		non_coding_transcript_exon_variant	Exon 1 of 4	5
ASAH1-AS1	ENST00000521775.6	n.809_811delTTT		non_coding_transcript_exon_variant	Exon 1 of 3	4
ASAH1-AS1	ENST00000702451.1	n.836_838delTTT		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7916 AN: 151004 Hom.: 366 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.00900

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0458 AC: 3898 AN: 85108 Hom.: 247 AF XY: 0.0531 AC XY: 2392 AN XY: 45074

Gnomad4 AFR exome AF: 0.0745

Gnomad4 AMR exome AF: 0.0803

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0131

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.0356

GnomAD4 genome AF: 0.0525 AC: 7939 AN: 151104 Hom.: 368 Cov.: 32 AF XY: 0.0556 AC XY: 4099 AN XY: 73766

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.00900

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0336 Hom.: 16

Bravo AF: 0.0563

Asia WGS AF: 0.153 AC: 532 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs34250229; hg19: chr8-17942723;