rs10088541

Positions:

• chr8-58618348-A-G
• chr8-58618348-A-T

Variant summary

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

The NM_003580.4(NSMAF):​c.557+4872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,816 control chromosomes in the GnomAD database, including 7,663 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 0.31 (7663 hom., cov: 31)
• Consequence: NSMAF NM_003580.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

Genes affected

NSMAF (HGNC:8017): (neutral sphingomyelinase activation associated factor) This gene encodes a WD-repeat protein that binds the cytoplasmic sphingomyelinase activation domain of the 55kD tumor necrosis factor receptor. This protein is required for TNF-mediated activation of neutral sphingomyelinase and may play a role in regulating TNF-induced cellular responses such as inflammation. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSMAF	NM_003580.4	c.557+4872T>C		intron_variant		ENST00000038176.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSMAF	ENST00000038176.8	c.557+4872T>C		intron_variant		1	NM_003580.4	P1
NSMAF	ENST00000427130.6	c.650+4872T>C		intron_variant		2
NSMAF	ENST00000649465.1	c.*683+4872T>C		intron_variant, NMD_transcript_variant
NSMAF	ENST00000519858.1	n.96+4872T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46785 AN: 151704 Hom.: 7662 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.308 AC: 46797 AN: 151816 Hom.: 7663 Cov.: 31 AF XY: 0.313 AC XY: 23257 AN XY: 74196

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.297

Alfa AF: 0.329 Hom.: 1067

Bravo AF: 0.289

Asia WGS AF: 0.301 AC: 1045 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.8
DANN	Benign	0.89

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: rs10088541; hg19: chr8-59530907;