rs945713

Variant names:

• chr1-162165880-G-A
• rs945713
• NM_014697.3:c.177+11404G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-162165880-G-A
• chr1-162165880-G-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.177+11404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,026 control chromosomes in the GnomAD database, including 18,635 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 (18635 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• 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)

LOC105371475 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+11404G>A		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+11404G>A		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+11404G>A		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+11404G>A		intron_variant	Intron 2 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.438+2402C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68192 AN: 151908 Hom.: 18636 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.449 AC: 68202 AN: 152026 Hom.: 18635 Cov.: 32 AF XY: 0.449 AC XY: 33398 AN XY: 74302

African (AFR) AF: 0.138 AC: 5739 AN: 41486

American (AMR) AF: 0.491 AC: 7502 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3466

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5158

South Asian (SAS) AF: 0.387 AC: 1863 AN: 4808

European-Finnish (FIN) AF: 0.654 AC: 6899 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41560 AN: 67970

Other (OTH) AF: 0.470 AC: 992 AN: 2112

Alfa AF: 0.556 Hom.: 12063

Bravo AF: 0.425

Asia WGS AF: 0.338 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.33
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: rs945713; hg19: chr1-162135670;