dbSNP rs35732828: NSF:c.*28C>A (chr17-46755851-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_006178.4(NSF):c.*28C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.136 in 1,606,416 control chromosomes in the GnomAD database, including 16,979 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 0.10 ( 1041 hom., cov: 31)

Exomes 𝑓: 0.14 ( 15938 hom. )

Consequence

NSF
NM_006178.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

Publications

29 publications found

Variant links:

Genes affected

NSF (HGNC:8016): (N-ethylmaleimide sensitive factor, vesicle fusing ATPase) Enables PDZ domain binding activity and ionotropic glutamate receptor binding activity. Involved in intracellular protein transport; positive regulation of protein catabolic process; and positive regulation of receptor recycling. Located in Golgi apparatus; cytosol; and plasma membrane. Implicated in developmental and epileptic encephalopathy. [provided by Alliance of Genome Resources, Apr 2022]

NSF links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NSF	NM_006178.4 link	c.*28C>A	3_prime_UTR_variant	Exon 21 of 21	ENST00000398238.8	NP_006169.2
NSF	NR_040116.2 link	n.2334C>A	non_coding_transcript_exon_variant	Exon 20 of 20
LRRC37A2	XM_024450773.2 link	c.4809+205332C>A	intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSF	ENST00000398238.8 link	c.*28C>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_006178.4	ENSP00000381293.4		P46459-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15248

AN:

151322

Hom.:

1041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.0723

Gnomad ASJ

AF:

0.0649

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0635

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.0877

GnomAD2 exomes

AF:

0.107

AC:

26242

AN:

245488

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0438

Gnomad ASJ exome

AF:

0.0595

Gnomad EAS exome

AF:

0.000224

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.140

AC:

203384

AN:

1454972

Hom.:

15938

Cov.:

AF XY:

0.138

AC XY:

99699

AN XY:

723920

show subpopulations

African (AFR)

AF:

0.0186

AC:

621

AN:

33374

American (AMR)

AF:

0.0462

AC:

2051

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.0610

AC:

1589

AN:

26052

East Asian (EAS)

AF:

0.000227

AC:

AN:

39674

South Asian (SAS)

AF:

0.0774

AC:

6603

AN:

85340

European-Finnish (FIN)

AF:

0.228

AC:

11911

AN:

52300

Middle Eastern (MID)

AF:

0.0389

AC:

224

AN:

5756

European-Non Finnish (NFE)

AF:

0.156

AC:

173161

AN:

1107896

Other (OTH)

AF:

0.120

AC:

7215

AN:

60154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

7365

14730

22095

29460

36825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6030

12060

18090

24120

30150

<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:

0.101

AC:

15246

AN:

151444

Hom.:

1041

Cov.:

AF XY:

0.104

AC XY:

7662

AN XY:

73916

show subpopulations

African (AFR)

AF:

0.0233

AC:

962

AN:

41276

American (AMR)

AF:

0.0723

AC:

1098

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.0649

AC:

225

AN:

3468

East Asian (EAS)

AF:

0.000583

AC:

AN:

5148

South Asian (SAS)

AF:

0.0635

AC:

304

AN:

4786

European-Finnish (FIN)

AF:

0.235

AC:

2452

AN:

10426

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9792

AN:

67868

Other (OTH)

AF:

0.0868

AC:

181

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

660

1321

1981

2642

3302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.119

Hom.:

997

Bravo

AF:

0.0843

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

4.1

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