1-162367380-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014697.3(NOS1AP):c.1434G>C(p.Ser478Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000628 in 1,608,352 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

NOS1AP
NM_014697.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.552

Publications

0 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:

ENSG00000254706 (HGNC:):

ENSG00000254706 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 1-162367380-G-C is Benign according to our data. Variant chr1-162367380-G-C is described in ClinVar as [Benign]. Clinvar id is 496431.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.552 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.1434G>C	p.Ser478Ser	synonymous_variant	Exon 10 of 10	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001164757.2 link	c.1419G>C	p.Ser473Ser	synonymous_variant	Exon 10 of 10		NP_001158229.1	O75052-3
NOS1AP	NM_001126060.2 link	c.549G>C	p.Ser183Ser	synonymous_variant	Exon 2 of 2		NP_001119532.2	O75052-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10 link	c.1434G>C	p.Ser478Ser	synonymous_variant	Exon 10 of 10	1	NM_014697.3	ENSP00000355133.5		O75052-1
ENSG00000254706	ENST00000420220.1 link	c.-12+176G>C		intron_variant	Intron 2 of 3	5		ENSP00000398035.1		F8W6W0

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000774

AC:

184

AN:

237750

AF XY:

0.000579

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.000237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000323

AC:

470

AN:

1455998

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

217

AN XY:

723806

show subpopulations

African (AFR)

AF:

0.0120

AC:

401

AN:

33384

American (AMR)

AF:

0.000339

AC:

AN:

44254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.0000701

AC:

AN:

85602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51996

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1109412

Other (OTH)

AF:

0.000682

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00354

AC:

540

AN:

152354

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0126

AC:

525

AN:

41588

American (AMR)

AF:

0.000523

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.00388

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 10, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The NOS1AP c.1434G>C (p.Ser478Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 100/76736 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.014939 (96/6426). This frequency is about 1494 times the estimated maximal expected allele frequency of a pathogenic NOS1AP variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. Taken together, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.5

(source)

DANN

Benign

0.78

PhyloP100

-0.55

PromoterAI

0.085

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(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.

1-162367380-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over