rs12029454

Variant names:

• chr1-162163327-G-A
• rs12029454
• NM_014697.3:c.177+8851G>A

Variant summary

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

The NM_014697.3(NOS1AP):​c.177+8851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,074 control chromosomes in the GnomAD database, including 3,798 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 0.21 (3798 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 45 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)

LOC105371475 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+8851G>A		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+8851G>A		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+8851G>A		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+8851G>A		intron_variant	Intron 2 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.438+4955C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32158 AN: 151958 Hom.: 3794 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.212 AC: 32178 AN: 152074 Hom.: 3798 Cov.: 32 AF XY: 0.217 AC XY: 16127 AN XY: 74328

African (AFR) AF: 0.289 AC: 11961 AN: 41454

American (AMR) AF: 0.218 AC: 3328 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1929 AN: 5162

South Asian (SAS) AF: 0.330 AC: 1593 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2065 AN: 10580

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10045 AN: 67990

Other (OTH) AF: 0.199 AC: 420 AN: 2106

Alfa AF: 0.172 Hom.: 12072

Bravo AF: 0.214

Asia WGS AF: 0.324 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.82
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: rs12029454; hg19: chr1-162133117;