ENST00000381733.9:c.126+164A>G

Variant names:

• chr8-18084512-T-C
• rs112230670
• ENST00000381733.9:c.126+164A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000381733.9(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 ENST00000381733.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14
• Publications: 0 publications found

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:55603): (ASAH1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381733.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH1	NM_004315.6		c.126+164A>G		intron	N/A	NP_004306.3
	ASAH1	NM_001127505.3		c.126+164A>G		intron	N/A	NP_001120977.1	Q13510-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH1	ENST00000381733.9	TSL:1	c.126+164A>G		intron	N/A	ENSP00000371152.4	Q13510-2
	ASAH1	ENST00000314146.10	TSL:1	c.126+164A>G		intron	N/A	ENSP00000326970.10	Q13510-3
	ASAH1	ENST00000637244.1	TSL:1	n.*65A>G		non_coding_transcript_exon	Exon 1 of 14	ENSP00000490188.1	A0A1B0GUP1

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

African (AFR) AF: 0.0730 AC: 2033 AN: 27840

American (AMR) AF: 0.00439 AC: 145 AN: 33036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21446

East Asian (EAS) AF: 0.00 AC: 0 AN: 33714

South Asian (SAS) AF: 0.0000846 AC: 6 AN: 70934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33912

Middle Eastern (MID) AF: 0.00357 AC: 13 AN: 3638

European-Non Finnish (NFE) AF: 0.000239 AC: 223 AN: 931682

Other (OTH) AF: 0.00495 AC: 253 AN: 51084

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

African (AFR) AF: 0.0720 AC: 2987 AN: 41486

American (AMR) AF: 0.00837 AC: 128 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68016

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0160 Hom.: 12

Bravo AF: 0.0232

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-1.1
PromoterAI		0.079	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs112230670; hg19: chr8-17942021;