1-162349734-A-G

Variant names:

• chr1-162349734-A-G
• rs11577628
• NM_014697.3:c.596-5453A>G

Variant summary

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

The ENST00000361897.10(NOS1AP):​c.596-5453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,230 control chromosomes in the GnomAD database, including 608 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 0.076 (608 hom., cov: 33)
• Consequence: NOS1AP ENST00000361897.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 13 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361897.10. 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.596-5453A>G		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.581-5453A>G		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.596-5453A>G		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.581-5453A>G		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.581-5453A>G		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11565 AN: 152112 Hom.: 609 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0606

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.0764

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

GnomAD4 genome AF: 0.0759 AC: 11558 AN: 152230 Hom.: 608 Cov.: 33 AF XY: 0.0793 AC XY: 5903 AN XY: 74432

African (AFR) AF: 0.0204 AC: 848 AN: 41552

American (AMR) AF: 0.0606 AC: 927 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3472

East Asian (EAS) AF: 0.0743 AC: 385 AN: 5184

South Asian (SAS) AF: 0.160 AC: 770 AN: 4810

European-Finnish (FIN) AF: 0.149 AC: 1581 AN: 10584

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0946 AC: 6437 AN: 68012

Other (OTH) AF: 0.0761 AC: 161 AN: 2116

Alfa AF: 0.0868 Hom.: 877

Bravo AF: 0.0661

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.058
DANN	Benign	0.68
PhyloP100		-0.20
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: rs11577628; hg19: chr1-162319524;