rs10088541

Variant names:

• chr8-58618348-A-G
• rs10088541
• NM_003580.4:c.557+4872T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003580.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSMAF	NM_003580.4	MANE Select	c.557+4872T>C		intron	N/A	NP_003571.2
	NSMAF	NM_001144772.1		c.650+4872T>C		intron	N/A	NP_001138244.1
	NSMAF	NM_001413006.1		c.626+4872T>C		intron	N/A	NP_001399935.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSMAF	ENST00000038176.8	TSL:1 MANE Select	c.557+4872T>C		intron	N/A	ENSP00000038176.3
	NSMAF	ENST00000427130.7	TSL:2	c.650+4872T>C		intron	N/A	ENSP00000411012.2
	NSMAF	ENST00000519858.1	TSL:3	n.96+4872T>C		intron	N/A

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

African (AFR) AF: 0.217 AC: 8998 AN: 41394

American (AMR) AF: 0.243 AC: 3707 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1573 AN: 5168

South Asian (SAS) AF: 0.311 AC: 1494 AN: 4806

European-Finnish (FIN) AF: 0.479 AC: 5034 AN: 10500

Middle Eastern (MID) AF: 0.269 AC: 78 AN: 290

European-Non Finnish (NFE) AF: 0.355 AC: 24095 AN: 67926

Other (OTH) AF: 0.297 AC: 625 AN: 2104

Alfa AF: 0.325 Hom.: 1084

Bravo AF: 0.289

Asia WGS AF: 0.301 AC: 1045 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.8
DANN	Benign	0.89
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10088541; hg19: chr8-59530907;