dbSNP rs11994937: NSMAF:c.1793-362G>A (chr8-58596021-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003580.4(NSMAF):c.1793-362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 204,394 control chromosomes in the GnomAD database, including 164 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 0.030 ( 129 hom., cov: 32)

Exomes 𝑓: 0.022 ( 35 hom. )

Consequence

NSMAF
NM_003580.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.811

Publications

8 publications found

Variant links:

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]

NSMAF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSMAF	NM_003580.4 link	c.1793-362G>A		intron_variant	Intron 21 of 30	ENST00000038176.8	NP_003571.2	Q92636-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSMAF	ENST00000038176.8 link	c.1793-362G>A		intron_variant	Intron 21 of 30	1	NM_003580.4	ENSP00000038176.3		Q92636-1

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4591

AN:

152086

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.0792

Gnomad SAS

AF:

0.0526

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.0263

GnomAD4 exome

AF:

0.0219

AC:

1141

AN:

52190

Hom.:

AF XY:

0.0249

AC XY:

731

AN XY:

29358

show subpopulations

African (AFR)

AF:

0.0531

AC:

AN:

1394

American (AMR)

AF:

0.00852

AC:

AN:

3288

Ashkenazi Jewish (ASJ)

AF:

0.00917

AC:

AN:

1200

East Asian (EAS)

AF:

0.0641

AC:

181

AN:

2824

South Asian (SAS)

AF:

0.0454

AC:

481

AN:

10594

European-Finnish (FIN)

AF:

0.00280

AC:

AN:

1784

Middle Eastern (MID)

AF:

0.00758

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.0113

AC:

326

AN:

28764

Other (OTH)

AF:

0.0154

AC:

AN:

2210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

110

164

219

274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0302

AC:

4591

AN:

152204

Hom.:

129

Cov.:

AF XY:

0.0298

AC XY:

2219

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0624

AC:

2590

AN:

41524

American (AMR)

AF:

0.0138

AC:

211

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

AN:

3470

East Asian (EAS)

AF:

0.0788

AC:

408

AN:

5176

South Asian (SAS)

AF:

0.0523

AC:

252

AN:

4822

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0148

AC:

1009

AN:

68008

Other (OTH)

AF:

0.0260

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

212

424

637

849

1061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0226

Hom.:

118

Bravo

AF:

0.0319

Asia WGS

AF:

0.0430

AC:

148

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

5.1

(source)

DANN

Benign

0.51

PhyloP100

0.81

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over