Genetic Variant NOS1AP:c.106-23908G>C (chr1-162130497-G-C) – 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.106-23908G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,918 control chromosomes in the GnomAD database, including 8,087 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 0.24 ( 8087 hom., cov: 32)

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Publications

5 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:

LOC105371475 (HGNC:):

LOC105371475 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=-0.72).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NOS1AP	NM_014697.3 link	c.106-23908G>C	intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2 link	c.106-23908G>C	intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066699.1 link	n.487-16595C>G	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NOS1AP	ENST00000361897.10 link	c.106-23908G>C	intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5 link	c.106-23908G>C	intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3 link	n.106-23908G>C	intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36051

AN:

151800

Hom.:

8069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0870

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.0843

Gnomad FIN

AF:

0.0794

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0973

Gnomad OTH

AF:

0.193

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

GnomAD4 genome

AF:

0.238

AC:

36111

AN:

151918

Hom.:

8087

Cov.:

AF XY:

0.231

AC XY:

17187

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.598

AC:

24671

AN:

41262

American (AMR)

AF:

0.120

AC:

1842

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0870

AC:

302

AN:

3472

East Asian (EAS)

AF:

0.176

AC:

912

AN:

5176

South Asian (SAS)

AF:

0.0835

AC:

403

AN:

4826

European-Finnish (FIN)

AF:

0.0794

AC:

841

AN:

10596

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0973

AC:

6613

AN:

67988

Other (OTH)

AF:

0.191

AC:

401

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1028

2057

3085

4114

5142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.0545

Hom.:

Bravo

AF:

0.257

Asia WGS

AF:

0.145

AC:

504

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.4

(source)

DANN

Benign

0.85

PhyloP100

-1.4

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