rs6995115

chr8-58586055-A-G

Variant summary

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

The NM_003580.4(NSMAF):c.2447-55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,360,804 control chromosomes in the GnomAD database, including 93,618 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 0.41 (13460 hom., cov: 32)
  • Exomes 𝑓: 0.36 (80158 hom.)
• Consequence: NSMAF NM_003580.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSMAF	NM_003580.4	c.2447-55T>C		intron_variant		ENST00000038176.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSMAF	ENST00000038176.8	c.2447-55T>C		intron_variant		1	NM_003580.4	P1
NSMAF	ENST00000427130.6	c.2540-55T>C		intron_variant		2
NSMAF	ENST00000649465.1	c.*2569-55T>C		intron_variant, NMD_transcript_variant
NSMAF	ENST00000521972.1	n.122-55T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62010 AN: 151880 Hom.: 13428 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.382

GnomAD4 exome AF: 0.359 AC: 434020 AN: 1208806 Hom.: 80158 AF XY: 0.361 AC XY: 221077 AN XY: 612228

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.408 AC: 62081 AN: 151998 Hom.: 13460 Cov.: 32 AF XY: 0.411 AC XY: 30570 AN XY: 74306

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.376

Alfa AF: 0.384 Hom.: 1442

Bravo AF: 0.405

Asia WGS AF: 0.447 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.022
Dann	Benign	0.52

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: rs6995115; hg19: chr8-59498614; COSMIC: COSV50683907; COSMIC: COSV50683907;