NM_014697.3:c.270+265T>C

Variant summary

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

The NM_014697.3(NOS1AP):​c.270+265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 151,338 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.076 ( 501 hom., cov: 32)

Consequence

NOS1AP
NM_014697.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 1-162287701-T-C is Benign according to our data. Variant chr1-162287701-T-C is described in ClinVar as [Benign]. Clinvar id is 1288060.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOS1APNM_014697.3 linkc.270+265T>C intron_variant Intron 3 of 9 ENST00000361897.10 NP_055512.1 O75052-1
NOS1APNM_001164757.2 linkc.270+265T>C intron_variant Intron 3 of 9 NP_001158229.1 O75052-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOS1APENST00000361897.10 linkc.270+265T>C intron_variant Intron 3 of 9 1 NM_014697.3 ENSP00000355133.5 O75052-1
NOS1APENST00000530878.5 linkc.270+265T>C intron_variant Intron 3 of 9 1 ENSP00000431586.1 O75052-3
NOS1APENST00000430120.3 linkn.270+265T>C intron_variant Intron 3 of 10 1 ENSP00000396713.3 E9PSG0

Frequencies

GnomAD3 genomes
AF:
0.0755
AC:
11423
AN:
151218
Hom.:
501
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0628
Gnomad AMI
AF:
0.289
Gnomad AMR
AF:
0.0691
Gnomad ASJ
AF:
0.139
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.0829
Gnomad FIN
AF:
0.0544
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.0867
Gnomad OTH
AF:
0.0845
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0756
AC:
11442
AN:
151338
Hom.:
501
Cov.:
32
AF XY:
0.0737
AC XY:
5442
AN XY:
73874
show subpopulations
Gnomad4 AFR
AF:
0.0630
Gnomad4 AMR
AF:
0.0691
Gnomad4 ASJ
AF:
0.139
Gnomad4 EAS
AF:
0.00136
Gnomad4 SAS
AF:
0.0838
Gnomad4 FIN
AF:
0.0544
Gnomad4 NFE
AF:
0.0867
Gnomad4 OTH
AF:
0.0836
Alfa
AF:
0.0171
Hom.:
7
Bravo
AF:
0.0781
Asia WGS
AF:
0.0390
AC:
140
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Apr 04, 2019
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.13
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs59636124; hg19: chr1-162257491; API