rs12048222

Variant names:

• chr1-162324304-A-G
• rs12048222
• NM_014697.3:c.345-8713A>G

Variant summary

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

The NM_014697.3(NOS1AP):​c.345-8713A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,874 control chromosomes in the GnomAD database, including 6,648 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 (6648 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986
• 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.345-8713A>G		intron_variant	Intron 4 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.330-8713A>G		intron_variant	Intron 4 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.345-8713A>G		intron_variant	Intron 4 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.330-8713A>G		intron_variant	Intron 4 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.330-8713A>G		intron_variant	Intron 4 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43240 AN: 151756 Hom.: 6640 Cov.: 31

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.285 AC: 43265 AN: 151874 Hom.: 6648 Cov.: 31 AF XY: 0.289 AC XY: 21473 AN XY: 74216

African (AFR) AF: 0.319 AC: 13202 AN: 41406

American (AMR) AF: 0.355 AC: 5425 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2791 AN: 5160

South Asian (SAS) AF: 0.219 AC: 1049 AN: 4800

European-Finnish (FIN) AF: 0.292 AC: 3068 AN: 10498

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15873 AN: 67954

Other (OTH) AF: 0.272 AC: 572 AN: 2100

Alfa AF: 0.254 Hom.: 3397

Bravo AF: 0.295

Asia WGS AF: 0.319 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		0.99
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: rs12048222; hg19: chr1-162294094;