Variant 1-162343728-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014697.3(NOS1AP):c.454-107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,317,090 control chromosomes in the GnomAD database, including 58,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 6999 hom., cov: 34)

Exomes 𝑓: 0.29 ( 51121 hom. )

Consequence

NOS1AP
NM_014697.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.384

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-162343728-A-G is Benign according to our data. Variant chr1-162343728-A-G is described in ClinVar as [Benign]. Clinvar id is 1234724.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3 linkuse as main transcript	c.454-107A>G		intron_variant		ENST00000361897.10
NOS1AP	NM_001164757.2 linkuse as main transcript	c.439-107A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10 linkuse as main transcript	c.454-107A>G	intron_variant	1	NM_014697.3		O75052-1
NOS1AP	ENST00000530878.5 linkuse as main transcript	c.439-107A>G	intron_variant	1		P1	O75052-3
NOS1AP	ENST00000430120.3 linkuse as main transcript	c.439-107A>G	intron_variant, NMD_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45154

AN:

152014

Hom.:

6986

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.304

GnomAD4 exome

AF:

0.289

AC:

337243

AN:

1164956

Hom.:

51121

AF XY:

0.290

AC XY:

172303

AN XY:

594102

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.436

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.503

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.325

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.297

AC:

45208

AN:

152134

Hom.:

6999

Cov.:

AF XY:

0.305

AC XY:

22661

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.534

Gnomad4 SAS

AF:

0.316

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.298

Hom.:

2397

Bravo

AF:

0.299

Asia WGS

AF:

0.372

AC:

1291

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.69

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over