Genetic Variant NM_014697.3:c.178-42661G>A (chr1-162244683-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.178-42661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,964 control chromosomes in the GnomAD database, including 6,158 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 0.28 ( 6158 hom., cov: 32)

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.740

Publications

7 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.178-42661G>A		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001164757.2 link	c.178-42661G>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.178-42661G>A	intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5	O75052-1
NOS1AP	ENST00000530878.5 link	c.178-42661G>A	intron_variant	Intron 2 of 9	1		ENSP00000431586.1	O75052-3
NOS1AP	ENST00000430120.3 link	n.178-42661G>A	intron_variant	Intron 2 of 10	1		ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42392

AN:

151846

Hom.:

6157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.274

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

GnomAD4 genome

AF:

0.279

AC:

42414

AN:

151964

Hom.:

6158

Cov.:

AF XY:

0.287

AC XY:

21296

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.265

AC:

10965

AN:

41444

American (AMR)

AF:

0.316

AC:

4811

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1006

AN:

3468

East Asian (EAS)

AF:

0.523

AC:

2693

AN:

5148

South Asian (SAS)

AF:

0.380

AC:

1832

AN:

4816

European-Finnish (FIN)

AF:

0.310

AC:

3270

AN:

10558

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16884

AN:

67970

Other (OTH)

AF:

0.279

AC:

588

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1540

3080

4619

6159

7699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.260

Hom.:

9139

Bravo

AF:

0.277

Asia WGS

AF:

0.420

AC:

1457

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.63

PhyloP100

-0.74

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