NM_014697.3:c.105+523G>C

Variant names:

• chr1-162070805-G-C
• rs1123217
• NM_014697.3:c.105+523G>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.105+523G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 152,010 control chromosomes in the GnomAD database, including 867 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 0.078 (867 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 4 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.105+523G>C		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.105+523G>C		intron_variant	Intron 1 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.105+523G>C		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.105+523G>C		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.105+523G>C		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11857 AN: 151892 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.00350

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0734

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

GnomAD4 genome AF: 0.0781 AC: 11876 AN: 152010 Hom.: 867 Cov.: 32 AF XY: 0.0744 AC XY: 5527 AN XY: 74282

African (AFR) AF: 0.199 AC: 8258 AN: 41432

American (AMR) AF: 0.0558 AC: 851 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0160 AC: 77 AN: 4808

European-Finnish (FIN) AF: 0.00350 AC: 37 AN: 10578

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0341 AC: 2321 AN: 67976

Other (OTH) AF: 0.0726 AC: 153 AN: 2106

Alfa AF: 0.0564 Hom.: 64

Bravo AF: 0.0872

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.59
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1123217; hg19: chr1-162040595;