rs347273

Variant names:

• chr1-162347723-G-A
• rs347273
• NM_014697.3:c.595+3747G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-162347723-G-A
• chr1-162347723-G-C
• chr1-162347723-G-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.595+3747G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,124 control chromosomes in the GnomAD database, including 53,095 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 0.83 (53095 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 14 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.595+3747G>A		intron_variant	Intron 6 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.580+3747G>A		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.595+3747G>A		intron_variant	Intron 6 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.580+3747G>A		intron_variant	Intron 6 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.580+3747G>A		intron_variant	Intron 6 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126627 AN: 152006 Hom.: 53057 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.833 AC: 126720 AN: 152124 Hom.: 53095 Cov.: 31 AF XY: 0.833 AC XY: 61922 AN XY: 74350

African (AFR) AF: 0.745 AC: 30896 AN: 41466

American (AMR) AF: 0.887 AC: 13564 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2976 AN: 3468

East Asian (EAS) AF: 0.925 AC: 4793 AN: 5180

South Asian (SAS) AF: 0.776 AC: 3740 AN: 4820

European-Finnish (FIN) AF: 0.834 AC: 8834 AN: 10588

Middle Eastern (MID) AF: 0.863 AC: 252 AN: 292

European-Non Finnish (NFE) AF: 0.870 AC: 59188 AN: 67996

Other (OTH) AF: 0.855 AC: 1809 AN: 2116

Alfa AF: 0.857 Hom.: 91835

Bravo AF: 0.836

Asia WGS AF: 0.839 AC: 2916 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	3.8
DANN	Benign	0.80
PhyloP100		-0.099
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: rs347273; hg19: chr1-162317513;