dbSNP rs12122048: NOS1AP:c.940-3786G>A (chr1-162361618-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.940-3786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,020 control chromosomes in the GnomAD database, including 9,129 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 0.34 ( 9129 hom., cov: 33)

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.215

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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.940-3786G>A		intron_variant	Intron 8 of 9	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001164757.2 link	c.925-3786G>A		intron_variant	Intron 8 of 9		NP_001158229.1	O75052-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOS1AP	ENST00000361897.10 link	c.940-3786G>A	intron_variant	Intron 8 of 9	1	NM_014697.3	ENSP00000355133.5	O75052-1
NOS1AP	ENST00000530878.5 link	c.925-3786G>A	intron_variant	Intron 8 of 9	1		ENSP00000431586.1	O75052-3
NOS1AP	ENST00000430120.3 link	n.1037+694G>A	intron_variant	Intron 9 of 10	1		ENSP00000396713.3	E9PSG0
NOS1AP	ENST00000464284.1 link	c.-94+694G>A	intron_variant	Intron 1 of 2	4		ENSP00000435711.1	E9PIP8

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

52005

AN:

151904

Hom.:

9119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.384

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

GnomAD4 genome

AF:

0.342

AC:

52042

AN:

152020

Hom.:

9129

Cov.:

AF XY:

0.338

AC XY:

25133

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.326

AC:

13504

AN:

41454

American (AMR)

AF:

0.310

AC:

4737

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1736

AN:

3466

East Asian (EAS)

AF:

0.194

AC:

1005

AN:

5168

South Asian (SAS)

AF:

0.415

AC:

1999

AN:

4816

European-Finnish (FIN)

AF:

0.286

AC:

3022

AN:

10560

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24691

AN:

67972

Other (OTH)

AF:

0.386

AC:

814

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1761

3522

5282

7043

8804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.358

Hom.:

29705

Bravo

AF:

0.340

Asia WGS

AF:

0.311

AC:

1084

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.77

(source)

DANN

Benign

0.35

PhyloP100

-0.21

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