rs347313

Variant names:

• chr1-162334486-A-G
• rs347313
• NM_014697.3:c.453+1361A>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.453+1361A>G 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 152,062 control chromosomes in the GnomAD database, including 16,457 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 (16457 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 17 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 = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.453+1361A>G		intron_variant	Intron 5 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.438+1361A>G		intron_variant	Intron 5 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.453+1361A>G		intron_variant	Intron 5 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.438+1361A>G		intron_variant	Intron 5 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.438+1361A>G		intron_variant	Intron 5 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68459 AN: 151944 Hom.: 16456 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.450 AC: 68464 AN: 152062 Hom.: 16457 Cov.: 32 AF XY: 0.442 AC XY: 32863 AN XY: 74304

African (AFR) AF: 0.304 AC: 12599 AN: 41496

American (AMR) AF: 0.455 AC: 6949 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1641 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1128 AN: 5176

South Asian (SAS) AF: 0.342 AC: 1651 AN: 4828

European-Finnish (FIN) AF: 0.463 AC: 4880 AN: 10544

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38098 AN: 67960

Other (OTH) AF: 0.479 AC: 1012 AN: 2114

Alfa AF: 0.521 Hom.: 42871

Bravo AF: 0.447

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.75
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: rs347313; hg19: chr1-162304276;