1-162285322-G-T

Variant names:

• chr1-162285322-G-T
• rs10800404
• NM_014697.3:c.178-2022G>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.178-2022G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,016 control chromosomes in the GnomAD database, including 6,772 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 0.29 (6772 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 5 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.178-2022G>T		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.178-2022G>T		intron	N/A	NP_001158229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.178-2022G>T		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.178-2022G>T		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.178-2022G>T		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43846 AN: 151898 Hom.: 6750 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.289 AC: 43921 AN: 152016 Hom.: 6772 Cov.: 32 AF XY: 0.296 AC XY: 22006 AN XY: 74304

African (AFR) AF: 0.304 AC: 12619 AN: 41456

American (AMR) AF: 0.355 AC: 5422 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3472

East Asian (EAS) AF: 0.593 AC: 3058 AN: 5156

South Asian (SAS) AF: 0.365 AC: 1753 AN: 4806

European-Finnish (FIN) AF: 0.271 AC: 2862 AN: 10578

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16103 AN: 67968

Other (OTH) AF: 0.292 AC: 615 AN: 2104

Alfa AF: 0.146 Hom.: 248

Bravo AF: 0.296

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		1.1
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: rs10800404; hg19: chr1-162255112;