rs7523798

Variant names:

• chr1-162177041-A-G
• rs7523798
• NM_014697.3:c.177+22565A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-162177041-A-G
• chr1-162177041-A-T

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+22565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,028 control chromosomes in the GnomAD database, including 22,713 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 0.52 (22713 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+22565A>G		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.177+22565A>G		intron_variant	Intron 2 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+22565A>G		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+22565A>G		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+22565A>G		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79339 AN: 151910 Hom.: 22688 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.522 AC: 79414 AN: 152028 Hom.: 22713 Cov.: 32 AF XY: 0.523 AC XY: 38851 AN XY: 74290

African (AFR) AF: 0.743 AC: 30804 AN: 41478

American (AMR) AF: 0.494 AC: 7547 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2000 AN: 3468

East Asian (EAS) AF: 0.761 AC: 3938 AN: 5176

South Asian (SAS) AF: 0.617 AC: 2967 AN: 4812

European-Finnish (FIN) AF: 0.372 AC: 3930 AN: 10568

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26657 AN: 67930

Other (OTH) AF: 0.512 AC: 1079 AN: 2106

Alfa AF: 0.452 Hom.: 13781

Bravo AF: 0.538

Asia WGS AF: 0.666 AC: 2319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.50
PhyloP100		-0.95
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: rs7523798; hg19: chr1-162146831;