dbSNP rs164147: NOS1AP:c.*1140A>C (chr1-162368607-A-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.*1140A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,198 control chromosomes in the GnomAD database, including 45,605 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 0.76 ( 45593 hom., cov: 34)

Exomes 𝑓: 0.96 ( 12 hom. )

Consequence

NOS1AP
NM_014697.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.423

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 links:

ENSG00000254706 (HGNC:):

ENSG00000254706 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3 link	c.*1140A>C	3_prime_UTR_variant	Exon 10 of 10	ENST00000361897.10	NP_055512.1	O75052-1
NOS1AP	NM_001164757.2 link	c.*1140A>C	3_prime_UTR_variant	Exon 10 of 10		NP_001158229.1	O75052-3
NOS1AP	NM_001126060.2 link	c.*1140A>C	3_prime_UTR_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.*1140A>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_014697.3	ENSP00000355133.5		O75052-1
ENSG00000254706	ENST00000420220.1 link	c.-12+1403A>C		intron_variant	Intron 2 of 3	5		ENSP00000398035.1		F8W6W0

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115545

AN:

152054

Hom.:

45585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.907

Gnomad AMR

AF:

0.816

Gnomad ASJ

AF:

0.843

Gnomad EAS

AF:

0.850

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.882

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.855

Gnomad OTH

AF:

0.798

GnomAD4 exome

AF:

0.962

AC:

AN:

Hom.:

Cov.:

AF XY:

0.944

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AC:

AN:

Gnomad4 SAS exome

AC:

AN:

Gnomad4 FIN exome

AF:

1.00

AC:

AN:

Gnomad4 NFE exome

AF:

1.00

AC:

AN:

Gnomad4 Remaining exome

AF:

0.750

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<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:

0.760

AC:

115583

AN:

152172

Hom.:

45593

Cov.:

AF XY:

0.760

AC XY:

56552

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.531

AC:

0.530834

AN:

0.530834

Gnomad4 AMR

AF:

0.816

AC:

0.816381

AN:

0.816381

Gnomad4 ASJ

AF:

0.843

AC:

0.843047

AN:

0.843047

Gnomad4 EAS

AF:

0.850

AC:

0.850348

AN:

0.850348

Gnomad4 SAS

AF:

0.725

AC:

0.724617

AN:

0.724617

Gnomad4 FIN

AF:

0.882

AC:

0.881909

AN:

0.881909

Gnomad4 NFE

AF:

0.855

AC:

0.855326

AN:

0.855326

Gnomad4 OTH

AF:

0.794

AC:

0.793756

AN:

0.793756

Heterozygous variant carriers

1290

2580

3869

5159

6449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.813

Hom.:

13517

Bravo

AF:

0.745

Asia WGS

AF:

0.749

AC:

2603

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.80

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over