rs4298709

Variant names:

• chr1-162266792-G-A
• rs4298709
• NM_014697.3:c.178-20552G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-162266792-G-A
• chr1-162266792-G-C

Variant summary

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

The NM_014697.3(NOS1AP):​c.178-20552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,984 control chromosomes in the GnomAD database, including 16,496 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 0.45 (16496 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.178-20552G>A		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.178-20552G>A		intron	N/A	NP_001158229.1	O75052-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.178-20552G>A		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.178-20552G>A		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.178-20552G>A		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68386 AN: 151866 Hom.: 16492 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.450 AC: 68403 AN: 151984 Hom.: 16496 Cov.: 32 AF XY: 0.446 AC XY: 33102 AN XY: 74278

African (AFR) AF: 0.313 AC: 12963 AN: 41452

American (AMR) AF: 0.400 AC: 6104 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3470

East Asian (EAS) AF: 0.170 AC: 878 AN: 5158

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4822

European-Finnish (FIN) AF: 0.565 AC: 5972 AN: 10568

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37813 AN: 67926

Other (OTH) AF: 0.461 AC: 973 AN: 2112

Alfa AF: 0.501 Hom.: 24738

Bravo AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		-0.044
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: rs4298709; hg19: chr1-162236582;