dbSNP rs6995115: NSMAF:c.2447-55T>C (chr8-58586055-A-G) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.66

Publications

6 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=-0.9).

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 rank	MANE	Protein	UniProt
NSMAF	NM_003580.4 link	c.2447-55T>C		intron_variant	Intron 28 of 30	ENST00000038176.8	NP_003571.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NSMAF	ENST00000038176.8 link	c.2447-55T>C	intron_variant	Intron 28 of 30	1	NM_003580.4	ENSP00000038176.3
NSMAF	ENST00000427130.7 link	c.2540-55T>C	intron_variant	Intron 28 of 30	2		ENSP00000411012.2
NSMAF	ENST00000521972.1 link	n.122-55T>C	intron_variant	Intron 1 of 2	5
NSMAF	ENST00000649465.1 link	n.*2569-55T>C	intron_variant	Intron 30 of 32			ENSP00000498107.1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

62010

AN:

151880

Hom.:

13428

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.562

AC:

16048

AN:

28540

American (AMR)

AF:

0.250

AC:

11076

AN:

44230

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7313

AN:

24486

East Asian (EAS)

AF:

0.579

AC:

22250

AN:

38412

South Asian (SAS)

AF:

0.413

AC:

33565

AN:

81236

European-Finnish (FIN)

AF:

0.396

AC:

19636

AN:

49644

Middle Eastern (MID)

AF:

0.309

AC:

1641

AN:

5310

European-Non Finnish (NFE)

AF:

0.343

AC:

303573

AN:

884950

Other (OTH)

AF:

0.364

AC:

18918

AN:

51998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

14424

28849

43273

57698

72122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9070

18140

27210

36280

45350

<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:

0.408

AC:

62081

AN:

151998

Hom.:

13460

Cov.:

AF XY:

0.411

AC XY:

30570

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.555

AC:

22979

AN:

41432

American (AMR)

AF:

0.302

AC:

4612

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

1026

AN:

3470

East Asian (EAS)

AF:

0.552

AC:

2852

AN:

5162

South Asian (SAS)

AF:

0.412

AC:

1988

AN:

4822

European-Finnish (FIN)

AF:

0.419

AC:

4422

AN:

10566

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.339

AC:

23025

AN:

67946

Other (OTH)

AF:

0.376

AC:

792

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1796

3593

5389

7186

8982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.390

Hom.:

1552

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

(source)

DANN

Benign

0.52

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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