rs880296

Variant names:

• chr1-162158656-G-C
• rs880296
• NM_014697.3:c.177+4180G>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+4180G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,058 control chromosomes in the GnomAD database, including 38,076 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 0.70 (38076 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+4180G>C		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.177+4180G>C		intron_variant	Intron 2 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.486+9626C>G		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.486+9626C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+4180G>C		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+4180G>C		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+4180G>C		intron_variant	Intron 2 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.438+9626C>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106227 AN: 151940 Hom.: 38031 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.699 AC: 106319 AN: 152058 Hom.: 38076 Cov.: 32 AF XY: 0.692 AC XY: 51417 AN XY: 74316

African (AFR) AF: 0.604 AC: 25041 AN: 41466

American (AMR) AF: 0.713 AC: 10916 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2549 AN: 3466

East Asian (EAS) AF: 0.405 AC: 2084 AN: 5140

South Asian (SAS) AF: 0.470 AC: 2265 AN: 4820

European-Finnish (FIN) AF: 0.709 AC: 7488 AN: 10564

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53520 AN: 67986

Other (OTH) AF: 0.718 AC: 1516 AN: 2110

Alfa AF: 0.750 Hom.: 5404

Bravo AF: 0.700

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.56
PhyloP100		-0.40
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: rs880296; hg19: chr1-162128446;