1-162342963-T-G

Variant names:

• chr1-162342963-T-G
• rs347282
• NM_014697.3:c.454-872T>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.454-872T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,030 control chromosomes in the GnomAD database, including 16,800 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 0.46 (16800 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.454-872T>G		intron_variant	Intron 5 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.439-872T>G		intron_variant	Intron 5 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.454-872T>G		intron_variant	Intron 5 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.439-872T>G		intron_variant	Intron 5 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.439-872T>G		intron_variant	Intron 5 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69281 AN: 151912 Hom.: 16787 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.456 AC: 69316 AN: 152030 Hom.: 16800 Cov.: 32 AF XY: 0.448 AC XY: 33289 AN XY: 74312

African (AFR) AF: 0.319 AC: 13229 AN: 41452

American (AMR) AF: 0.458 AC: 6999 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1645 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1127 AN: 5160

South Asian (SAS) AF: 0.342 AC: 1650 AN: 4820

European-Finnish (FIN) AF: 0.463 AC: 4892 AN: 10558

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38244 AN: 67972

Other (OTH) AF: 0.484 AC: 1020 AN: 2108

Alfa AF: 0.526 Hom.: 83019

Bravo AF: 0.453

Asia WGS AF: 0.312 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.82
PhyloP100		-0.093
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: rs347282; hg19: chr1-162312753;