rs10508923

Variant names:

• chr10-50272264-G-A
• rs10508923
• ENST00000395526.9:c.-154+7319C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395526.9(ASAH2):​c.-154+7319C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 152,214 control chromosomes in the GnomAD database, including 547 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 0.051 (547 hom., cov: 32)
• Consequence: ASAH2 ENST00000395526.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASAH2	ENST00000395526.9	c.-154+7319C>T		intron_variant	Intron 1 of 21	1		ENSP00000378897.3

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7801 AN: 152096 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0514 AC: 7822 AN: 152214 Hom.: 547 Cov.: 32 AF XY: 0.0548 AC XY: 4080 AN XY: 74412

African (AFR) AF: 0.0881 AC: 3659 AN: 41520

American (AMR) AF: 0.0421 AC: 643 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1784 AN: 5172

South Asian (SAS) AF: 0.116 AC: 559 AN: 4824

European-Finnish (FIN) AF: 0.0317 AC: 336 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 691 AN: 68028

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

Alfa AF: 0.0228 Hom.: 179

Bravo AF: 0.0550

Asia WGS AF: 0.209 AC: 724 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.93
DANN	Benign	0.46
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs10508923; hg19: chr10-52032024;