NM_019893.4:c.-37+447G>A

Variant names:

• chr10-50250948-C-T
• rs10508921
• NM_019893.4:c.-37+447G>A

Variant summary

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

The NM_019893.4(ASAH2):​c.-37+447G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,146 control chromosomes in the GnomAD database, including 1,014 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 0.10 (1014 hom., cov: 32)
• Consequence: ASAH2 NM_019893.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019893.4. 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
	ASAH2	NM_019893.4	MANE Select	c.-37+447G>A		intron	N/A	NP_063946.2
	ASAH2	NM_001143974.3		c.-37+447G>A		intron	N/A	NP_001137446.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH2	ENST00000682911.1	MANE Select	c.-37+447G>A		intron	N/A	ENSP00000506746.1
	ASAH2	ENST00000395526.9	TSL:1	c.-37+447G>A		intron	N/A	ENSP00000378897.3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15348 AN: 152028 Hom.: 1011 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0950

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.101 AC: 15355 AN: 152146 Hom.: 1014 Cov.: 32 AF XY: 0.105 AC XY: 7802 AN XY: 74376

African (AFR) AF: 0.105 AC: 4363 AN: 41490

American (AMR) AF: 0.0877 AC: 1339 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5174

South Asian (SAS) AF: 0.191 AC: 921 AN: 4824

European-Finnish (FIN) AF: 0.0950 AC: 1006 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5380 AN: 68004

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.0911 Hom.: 1375

Bravo AF: 0.101

Asia WGS AF: 0.251 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.62
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs10508921; hg19: chr10-52010708;