dbSNP rs4657161: NOS1AP:c.177+32023G>A (chr1-162186499-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.177+32023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,912 control chromosomes in the GnomAD database, including 18,844 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 0.47 ( 18844 hom., cov: 32)

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839

Publications

3 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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.177+32023G>A		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001164757.2 link	c.177+32023G>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.177+32023G>A	intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5	O75052-1
NOS1AP	ENST00000530878.5 link	c.177+32023G>A	intron_variant	Intron 2 of 9	1		ENSP00000431586.1	O75052-3
NOS1AP	ENST00000430120.3 link	n.177+32023G>A	intron_variant	Intron 2 of 10	1		ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70789

AN:

151798

Hom.:

18841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.618

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.608

Gnomad OTH

AF:

0.482

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

GnomAD4 genome

AF:

0.466

AC:

70821

AN:

151912

Hom.:

18844

Cov.:

AF XY:

0.466

AC XY:

34574

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.216

AC:

8938

AN:

41414

American (AMR)

AF:

0.500

AC:

7641

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1484

AN:

3468

East Asian (EAS)

AF:

0.239

AC:

1238

AN:

5170

South Asian (SAS)

AF:

0.382

AC:

1830

AN:

4796

European-Finnish (FIN)

AF:

0.631

AC:

6651

AN:

10546

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.608

AC:

41310

AN:

67930

Other (OTH)

AF:

0.480

AC:

1012

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1742

3484

5226

6968

8710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.531

Hom.:

3080

Bravo

AF:

0.448

Asia WGS

AF:

0.325

AC:

1130

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

0.60

(source)

DANN

Benign

0.48

PhyloP100

-0.84

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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