rs7508

Variant names:

• chr8-18056461-G-A
• rs7508
• NM_177924.5:c.*1073C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-18056461-G-A
• chr8-18056461-G-C
• chr8-18056461-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177924.5(ASAH1):​c.*1073C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,126 control chromosomes in the GnomAD database, including 44,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44951 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ASAH1 NM_177924.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.72
• Publications: 40 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 Gene-Disease associations (from GenCC):

• ASAH1-related sphingolipidosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Farber lipogranulomatosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• spinal muscular atrophy-progressive myoclonic epilepsy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-18056461-G-A is Benign according to our data. Variant chr8-18056461-G-A is described in ClinVar as Benign. ClinVar VariationId is 362350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177924.5. 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_177924.5	MANE Select	c.*1073C>T		3_prime_UTR	Exon 14 of 14	NP_808592.2	Q13510-1
	ASAH1	NM_004315.6		c.*1073C>T		3_prime_UTR	Exon 14 of 14	NP_004306.3
	ASAH1	NM_001127505.3		c.*1073C>T		3_prime_UTR	Exon 14 of 14	NP_001120977.1	Q13510-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH1	ENST00000637790.2	TSL:1 MANE Select	c.*1073C>T		3_prime_UTR	Exon 14 of 14	ENSP00000490272.1	Q13510-1
	ASAH1	ENST00000381733.9	TSL:1	c.*1073C>T		3_prime_UTR	Exon 14 of 14	ENSP00000371152.4	Q13510-2
	ASAH1	ENST00000637528.1	TSL:5	c.*1073C>T		splice_region	Exon 14 of 14	ENSP00000490801.1	A0A1B0GW68

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115859 AN: 152004 Hom.: 44914 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.762 AC: 115945 AN: 152122 Hom.: 44951 Cov.: 32 AF XY: 0.756 AC XY: 56237 AN XY: 74366

African (AFR) AF: 0.918 AC: 38113 AN: 41524

American (AMR) AF: 0.679 AC: 10373 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2415 AN: 3464

East Asian (EAS) AF: 0.560 AC: 2888 AN: 5160

South Asian (SAS) AF: 0.662 AC: 3193 AN: 4820

European-Finnish (FIN) AF: 0.708 AC: 7476 AN: 10564

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 49035 AN: 68002

Other (OTH) AF: 0.741 AC: 1564 AN: 2112

Alfa AF: 0.730 Hom.: 173705

Bravo AF: 0.763

Asia WGS AF: 0.638 AC: 2222 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.011
DANN	Benign	0.44
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7508; hg19: chr8-17913970;