rs1982082

Variant names:

• chr19-6322431-C-T
• rs1982082
• NM_133492.3:c.94-9932G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133492.3(ACER1):​c.94-9932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,864 control chromosomes in the GnomAD database, including 32,893 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32893 hom., cov: 30)
• Consequence: ACER1 NM_133492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

ACER1 (HGNC:18356): (alkaline ceramidase 1) Ceramides are synthesized during epidermal differentiation and accumulate within the interstices of the stratum corneum, where they represent critical components of the epidermal permeability barrier. Excess cellular ceramide can trigger antimitogenic signals and induce apoptosis, and the ceramide metabolites sphingosine and sphingosine-1-phosphate (S1P) are important bioregulatory molecules. Ceramide hydrolysis in the nucleated cell layers regulates keratinocyte proliferation and apoptosis in response to external stress. Ceramide hydrolysis also occurs at the stratum corneum, releasing free sphingoid base that functions as an endogenous antimicrobial agent. ACER1 is highly expressed in epidermis and catalyzes the hydrolysis of very long chain ceramides to generate sphingosine (Houben et al., 2006 [PubMed 16477081]; Sun et al., 2008 [PubMed 17713573]).[supplied by OMIM, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACER1	NM_133492.3	c.94-9932G>A		intron_variant	Intron 1 of 5	ENST00000301452.5	NP_597999.1
ACER1	XM_011527673.3	c.-36-9932G>A		intron_variant	Intron 2 of 6		XP_011525975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACER1	ENST00000301452.5	c.94-9932G>A		intron_variant	Intron 1 of 5	1	NM_133492.3	ENSP00000301452.3

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98643 AN: 151746 Hom.: 32848 Cov.: 30

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.634

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.650 AC: 98754 AN: 151864 Hom.: 32893 Cov.: 30 AF XY: 0.648 AC XY: 48058 AN XY: 74168

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.635

Alfa AF: 0.600 Hom.: 41844

Bravo AF: 0.650

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1982082; hg19: chr19-6322442;