rs347311

Variant names:

• chr1-162334117-G-C
• rs347311
• NM_014697.3:c.453+992G>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.453+992G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,160 control chromosomes in the GnomAD database, including 3,853 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 0.20 (3853 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.453+992G>C		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.438+992G>C		intron	N/A	NP_001158229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.453+992G>C		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.438+992G>C		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.438+992G>C		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30682 AN: 152042 Hom.: 3852 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.202 AC: 30673 AN: 152160 Hom.: 3853 Cov.: 32 AF XY: 0.198 AC XY: 14748 AN XY: 74370

African (AFR) AF: 0.0566 AC: 2349 AN: 41530

American (AMR) AF: 0.231 AC: 3538 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3470

East Asian (EAS) AF: 0.160 AC: 827 AN: 5172

South Asian (SAS) AF: 0.170 AC: 818 AN: 4814

European-Finnish (FIN) AF: 0.244 AC: 2578 AN: 10574

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19409 AN: 67984

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.242 Hom.: 685

Bravo AF: 0.199

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.48
PhyloP100		-0.34
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: rs347311; hg19: chr1-162303907;