Variant rs905721 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000361897.10(NOS1AP):c.940-142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,507,558 control chromosomes in the GnomAD database, including 100,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8491 hom., cov: 33)

Exomes 𝑓: 0.36 ( 92358 hom. )

Consequence

NOS1AP
ENST00000361897.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0430

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-162365262-C-T is Benign according to our data. Variant chr1-162365262-C-T is described in ClinVar as [Benign]. Clinvar id is 1238681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
NOS1AP	NM_014697.3 linkuse as main transcript	c.940-142C>T	intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001126060.2 linkuse as main transcript	c.-88C>T	5_prime_UTR_variant	1/2		NP_001119532.2
NOS1AP	NM_001164757.2 linkuse as main transcript	c.925-142C>T	intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10 linkuse as main transcript	c.940-142C>T		intron_variant		1	NM_014697.3	ENSP00000355133		O75052-1

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47134

AN:

152010

Hom.:

8483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.322

GnomAD4 exome

AF:

0.364

AC:

493390

AN:

1355430

Hom.:

92358

Cov.:

AF XY:

0.361

AC XY:

239382

AN XY:

662908

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.435

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.506

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.345

GnomAD4 genome

AF:

0.310

AC:

47141

AN:

152128

Hom.:

8491

Cov.:

AF XY:

0.315

AC XY:

23408

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.522

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.445

Gnomad4 NFE

AF:

0.371

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.341

Hom.:

1204

Bravo

AF:

0.303

Asia WGS

AF:

0.347

AC:

1206

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.6

DANN

Benign

0.78

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