dbSNP rs1538018: NOS1AP:c.177+6215G>C (chr1-162160691-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.177+6215G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,052 control chromosomes in the GnomAD database, including 3,934 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 0.22 ( 3934 hom., cov: 32)

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

6 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.177+6215G>C		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1	O75052-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOS1AP	ENST00000361897.10 link	c.177+6215G>C	intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5	O75052-1
NOS1AP	ENST00000530878.5 link	c.177+6215G>C	intron_variant	Intron 2 of 9	1		ENSP00000431586.1	O75052-3
NOS1AP	ENST00000430120.3 link	n.177+6215G>C	intron_variant	Intron 2 of 10	1		ENSP00000396713.3	E9PSG0
ENSG00000285636	ENST00000648032.1 link	n.438+7591C>G	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34089

AN:

151934

Hom.:

3935

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.223

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

GnomAD4 genome

AF:

0.224

AC:

34105

AN:

152052

Hom.:

3934

Cov.:

AF XY:

0.220

AC XY:

16355

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.209

AC:

8676

AN:

41470

American (AMR)

AF:

0.211

AC:

3221

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1040

AN:

3472

East Asian (EAS)

AF:

0.165

AC:

852

AN:

5172

South Asian (SAS)

AF:

0.203

AC:

979

AN:

4824

European-Finnish (FIN)

AF:

0.188

AC:

1985

AN:

10556

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.245

AC:

16647

AN:

67972

Other (OTH)

AF:

0.221

AC:

467

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1391

2782

4173

5564

6955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.234

Hom.:

577

Bravo

AF:

0.227

Asia WGS

AF:

0.163

AC:

572

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

(source)

DANN

Benign

0.48

PhyloP100

0.027

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