chr1-162340523-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014697.3(NOS1AP):​c.454-3312T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,212 control chromosomes in the GnomAD database, including 6,295 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 0.28 ( 6295 hom., cov: 33)

Consequence

NOS1AP
NM_014697.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.165
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOS1APNM_014697.3 linkuse as main transcriptc.454-3312T>C intron_variant ENST00000361897.10 NP_055512.1
NOS1APNM_001164757.2 linkuse as main transcriptc.439-3312T>C intron_variant NP_001158229.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOS1APENST00000361897.10 linkuse as main transcriptc.454-3312T>C intron_variant 1 NM_014697.3 ENSP00000355133 O75052-1
NOS1APENST00000530878.5 linkuse as main transcriptc.439-3312T>C intron_variant 1 ENSP00000431586 P1O75052-3
NOS1APENST00000430120.3 linkuse as main transcriptc.439-3312T>C intron_variant, NMD_transcript_variant 1 ENSP00000396713

Frequencies

GnomAD3 genomes
AF:
0.278
AC:
42296
AN:
152094
Hom.:
6285
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.209
Gnomad AMI
AF:
0.284
Gnomad AMR
AF:
0.372
Gnomad ASJ
AF:
0.296
Gnomad EAS
AF:
0.528
Gnomad SAS
AF:
0.280
Gnomad FIN
AF:
0.327
Gnomad MID
AF:
0.171
Gnomad NFE
AF:
0.272
Gnomad OTH
AF:
0.284
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.278
AC:
42331
AN:
152212
Hom.:
6295
Cov.:
33
AF XY:
0.286
AC XY:
21257
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.209
Gnomad4 AMR
AF:
0.373
Gnomad4 ASJ
AF:
0.296
Gnomad4 EAS
AF:
0.527
Gnomad4 SAS
AF:
0.281
Gnomad4 FIN
AF:
0.327
Gnomad4 NFE
AF:
0.272
Gnomad4 OTH
AF:
0.283
Alfa
AF:
0.268
Hom.:
5494
Bravo
AF:
0.278
Asia WGS
AF:
0.352
AC:
1222
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
4.0
DANN
Benign
0.65

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: rs10800465; hg19: chr1-162310313; API