dbSNP rs6664501: NOS1AP:c.105+8741C>G (chr1-162079023-C-G) – 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.105+8741C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,206 control chromosomes in the GnomAD database, including 1,945 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 0.087 ( 1945 hom., cov: 32)

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.566

Publications

1 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.105+8741C>G		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2 link	c.105+8741C>G		intron_variant	Intron 1 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NOS1AP	ENST00000361897.10 link	c.105+8741C>G	intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5 link	c.105+8741C>G	intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3 link	n.105+8741C>G	intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes

AF:

0.0873

AC:

13271

AN:

152088

Hom.:

1941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.0631

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

GnomAD4 genome

AF:

0.0874

AC:

13303

AN:

152206

Hom.:

1945

Cov.:

AF XY:

0.0837

AC XY:

6230

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.302

AC:

12534

AN:

41476

American (AMR)

AF:

0.0343

AC:

524

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00141

AC:

AN:

68022

Other (OTH)

AF:

0.0624

AC:

132

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

477

954

1430

1907

2384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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.:

149

Bravo

AF:

0.0991

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.6

(source)

DANN

Benign

0.40

PhyloP100

0.57

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