rs1858232

Variant names:

• chr1-162334048-A-G
• rs1858232
• NM_014697.3:c.453+923A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-162334048-A-G
• chr1-162334048-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.453+923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,038 control chromosomes in the GnomAD database, including 6,370 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 (6370 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 22

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.453+923A>G		intron_variant	Intron 5 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.438+923A>G		intron_variant	Intron 5 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.453+923A>G		intron_variant	Intron 5 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.438+923A>G		intron_variant	Intron 5 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.438+923A>G		intron_variant	Intron 5 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42450 AN: 151920 Hom.: 6360 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42483 AN: 152038 Hom.: 6370 Cov.: 32 AF XY: 0.287 AC XY: 21324 AN XY: 74300

African (AFR) AF: 0.208 AC: 8622 AN: 41496

American (AMR) AF: 0.374 AC: 5716 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2863 AN: 5168

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3456 AN: 10548

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18513 AN: 67960

Other (OTH) AF: 0.284 AC: 600 AN: 2110

Alfa AF: 0.271 Hom.: 8634

Bravo AF: 0.280

Asia WGS AF: 0.365 AC: 1266 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	1.0
DANN	Benign	0.74
PhyloP100		-0.73
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

Other links and lift over

dbSNP: rs1858232; hg19: chr1-162303838;