Genetic Variant ENST00000493151.1:c.-1150A>G (chr1-162364200-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000493151.1(NOS1AP):c.-1150A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 985,208 control chromosomes in the GnomAD database, including 62,388 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 0.34 ( 8801 hom., cov: 32)

Exomes 𝑓: 0.36 ( 53587 hom. )

Consequence

NOS1AP
ENST00000493151.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.785

Publications

11 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.940-1204A>G	intron_variant	Intron 8 of 9	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001126060.2 link	c.-1150A>G	5_prime_UTR_variant	Exon 1 of 2		NP_001119532.2	O75052-2
NOS1AP	NM_001164757.2 link	c.925-1204A>G	intron_variant	Intron 8 of 9		NP_001158229.1	O75052-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10 link	c.940-1204A>G		intron_variant	Intron 8 of 9	1	NM_014697.3	ENSP00000355133.5		O75052-1

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

50983

AN:

151958

Hom.:

8800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.381

GnomAD4 exome

AF:

0.358

AC:

298063

AN:

833128

Hom.:

53587

Cov.:

AF XY:

0.358

AC XY:

137653

AN XY:

384724

show subpopulations

African (AFR)

AF:

0.321

AC:

5063

AN:

15786

American (AMR)

AF:

0.280

AC:

276

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

2501

AN:

5154

East Asian (EAS)

AF:

0.207

AC:

750

AN:

3630

South Asian (SAS)

AF:

0.398

AC:

6543

AN:

16460

European-Finnish (FIN)

AF:

0.331

AC:

AN:

296

Middle Eastern (MID)

AF:

0.444

AC:

720

AN:

1620

European-Non Finnish (NFE)

AF:

0.357

AC:

272302

AN:

761898

Other (OTH)

AF:

0.359

AC:

9810

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

10575

21150

31725

42300

52875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11914

23828

35742

47656

59570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.335

AC:

50998

AN:

152080

Hom.:

8801

Cov.:

AF XY:

0.330

AC XY:

24570

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.310

AC:

12867

AN:

41486

American (AMR)

AF:

0.308

AC:

4713

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1736

AN:

3472

East Asian (EAS)

AF:

0.193

AC:

998

AN:

5164

South Asian (SAS)

AF:

0.377

AC:

1815

AN:

4820

European-Finnish (FIN)

AF:

0.282

AC:

2980

AN:

10586

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.361

AC:

24557

AN:

67964

Other (OTH)

AF:

0.381

AC:

803

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1770

3540

5310

7080

8850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.358

Hom.:

16315

Bravo

AF:

0.334

Asia WGS

AF:

0.281

AC:

980

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

(source)

DANN

Benign

0.69

PhyloP100

-0.79

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over