chr1-162353165-C-T

Variant names:

• chr1-162353165-C-T
• rs12403202
• NM_014697.3:c.596-2022C>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.596-2022C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,960 control chromosomes in the GnomAD database, including 3,324 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 0.19 (3324 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.596-2022C>T		intron_variant	Intron 6 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.581-2022C>T		intron_variant	Intron 6 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.596-2022C>T		intron_variant	Intron 6 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.581-2022C>T		intron_variant	Intron 6 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.581-2022C>T		intron_variant	Intron 6 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28722 AN: 151842 Hom.: 3323 Cov.: 31

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.189 AC: 28735 AN: 151960 Hom.: 3324 Cov.: 31 AF XY: 0.189 AC XY: 14019 AN XY: 74256

African (AFR) AF: 0.0661 AC: 2740 AN: 41454

American (AMR) AF: 0.184 AC: 2810 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3470

East Asian (EAS) AF: 0.188 AC: 970 AN: 5162

South Asian (SAS) AF: 0.142 AC: 685 AN: 4808

European-Finnish (FIN) AF: 0.310 AC: 3258 AN: 10504

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17155 AN: 67964

Other (OTH) AF: 0.175 AC: 368 AN: 2108

Alfa AF: 0.229 Hom.: 7837

Bravo AF: 0.175

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.25
PhyloP100		-0.076
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: rs12403202; hg19: chr1-162322955;