rs2043618

chr10-50247011-G-C

Variant summary

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

The NM_019893.4(ASAH2):c.127+1473C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,030 control chromosomes in the GnomAD database, including 6,614 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 0.29 (6614 hom., cov: 31)
• Consequence: ASAH2 NM_019893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493

Genes affected

ASAH2 (HGNC:18860): (N-acylsphingosine amidohydrolase 2) Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosphorylated form functions as an intra- and intercellular second messenger (see MIM 603730) (Mitsutake et al., 2001 [PubMed 11328816]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASAH2	NM_019893.4	c.127+1473C>G		intron_variant		ENST00000682911.1
ASAH2	NM_001143974.3	c.127+1473C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASAH2	ENST00000682911.1	c.127+1473C>G		intron_variant			NM_019893.4	P1
ASAH2	ENST00000329428.10	c.70+1473C>G		intron_variant		1
ASAH2	ENST00000395526.9	c.127+1473C>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43953 AN: 151912 Hom.: 6616 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.289 AC: 43967 AN: 152030 Hom.: 6614 Cov.: 31 AF XY: 0.286 AC XY: 21237 AN XY: 74314

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.298

Alfa AF: 0.307 Hom.: 899

Bravo AF: 0.282

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.8
Dann	Benign	0.66

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: rs2043618; hg19: chr10-52006771;