rs10918762

Variant names:

• chr1-162149194-A-G
• rs10918762
• NM_014697.3:c.106-5211A>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.106-5211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,148 control chromosomes in the GnomAD database, including 5,715 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 0.26 (5715 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• 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)

ENSG00000285636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-5211A>G		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-5211A>G		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.487-16068T>C		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.486+19088T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-5211A>G		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-5211A>G		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-5211A>G		intron_variant	Intron 1 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.439-1476T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39340 AN: 152030 Hom.: 5712 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.259 AC: 39336 AN: 152148 Hom.: 5715 Cov.: 33 AF XY: 0.267 AC XY: 19862 AN XY: 74360

African (AFR) AF: 0.257 AC: 10673 AN: 41522

American (AMR) AF: 0.268 AC: 4096 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3466

East Asian (EAS) AF: 0.595 AC: 3077 AN: 5170

South Asian (SAS) AF: 0.512 AC: 2467 AN: 4822

European-Finnish (FIN) AF: 0.288 AC: 3051 AN: 10588

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14292 AN: 67968

Other (OTH) AF: 0.244 AC: 515 AN: 2114

Alfa AF: 0.228 Hom.: 17150

Bravo AF: 0.251

Asia WGS AF: 0.509 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.45
PhyloP100		0.074
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: rs10918762; hg19: chr1-162118984;