1-162156654-A-G

Variant names:

• chr1-162156654-A-G
• rs951121
• NM_014697.3:c.177+2178A>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.177+2178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,104 control chromosomes in the GnomAD database, including 45,689 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 0.76 (45689 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• 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)

ENSG00000285636 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+2178A>G		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.177+2178A>G		intron_variant	Intron 2 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.486+11628T>C		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.486+11628T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+2178A>G		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+2178A>G		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+2178A>G		intron_variant	Intron 2 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.439-8936T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115549 AN: 151984 Hom.: 45674 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.760 AC: 115600 AN: 152104 Hom.: 45689 Cov.: 31 AF XY: 0.768 AC XY: 57110 AN XY: 74396

African (AFR) AF: 0.524 AC: 21715 AN: 41412

American (AMR) AF: 0.857 AC: 13095 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2694 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4275 AN: 5184

South Asian (SAS) AF: 0.850 AC: 4090 AN: 4812

European-Finnish (FIN) AF: 0.937 AC: 9944 AN: 10616

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57137 AN: 68006

Other (OTH) AF: 0.792 AC: 1674 AN: 2114

Alfa AF: 0.815 Hom.: 86530

Bravo AF: 0.742

Asia WGS AF: 0.829 AC: 2878 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	0.67
DANN	Benign	0.58
PhyloP100		-0.19
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: rs951121; hg19: chr1-162126444;