dbSNP rs12733377: NOS1AP:c.178-4691G>A (chr1-162282653-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014697.3(NOS1AP):c.178-4691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,088 control chromosomes in the GnomAD database, including 13,903 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 0.38 ( 13903 hom., cov: 32)

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

6 publications found

Variant links:

Genes affected

NOS1AP (HGNC:16859): (nitric oxide synthase 1 adaptor protein) This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2009]

NOS1AP Gene-Disease associations (from GenCC):

nephrotic syndrome, type 22
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NOS1AP 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.178-4691G>A		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001164757.2 link	c.178-4691G>A		intron_variant	Intron 2 of 9		NP_001158229.1	O75052-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOS1AP	ENST00000361897.10 link	c.178-4691G>A	intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5	O75052-1
NOS1AP	ENST00000530878.5 link	c.178-4691G>A	intron_variant	Intron 2 of 9	1		ENSP00000431586.1	O75052-3
NOS1AP	ENST00000430120.3 link	n.178-4691G>A	intron_variant	Intron 2 of 10	1		ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57520

AN:

151970

Hom.:

13906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.0297

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.378

AC:

57512

AN:

152088

Hom.:

13903

Cov.:

AF XY:

0.376

AC XY:

27954

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.111

AC:

4607

AN:

41516

American (AMR)

AF:

0.360

AC:

5501

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1405

AN:

3470

East Asian (EAS)

AF:

0.0296

AC:

153

AN:

5176

South Asian (SAS)

AF:

0.330

AC:

1585

AN:

4810

European-Finnish (FIN)

AF:

0.582

AC:

6144

AN:

10554

Middle Eastern (MID)

AF:

0.432

AC:

126

AN:

292

European-Non Finnish (NFE)

AF:

0.542

AC:

36857

AN:

67966

Other (OTH)

AF:

0.393

AC:

828

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1491

2982

4474

5965

7456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.471

Hom.:

10127

Bravo

AF:

0.351

Asia WGS

AF:

0.169

AC:

588

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.3

(source)

DANN

Benign

0.55

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over