1-162285595-A-T

Variant names:

• chr1-162285595-A-T
• rs4657181
• NM_014697.3:c.178-1749A>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.178-1749A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 139,232 control chromosomes in the GnomAD database, including 14,332 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 0.42 (14332 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-1749A>T		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-1749A>T		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.178-1749A>T		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-1749A>T		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-1749A>T		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 58393 AN: 139142 Hom.: 14335 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0446

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.419 AC: 58386 AN: 139232 Hom.: 14332 Cov.: 31 AF XY: 0.419 AC XY: 28346 AN XY: 67592

African (AFR) AF: 0.125 AC: 4686 AN: 37478

American (AMR) AF: 0.410 AC: 5524 AN: 13470

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1415 AN: 3256

East Asian (EAS) AF: 0.0444 AC: 156 AN: 3512

South Asian (SAS) AF: 0.386 AC: 1592 AN: 4124

European-Finnish (FIN) AF: 0.625 AC: 6155 AN: 9852

Middle Eastern (MID) AF: 0.478 AC: 129 AN: 270

European-Non Finnish (NFE) AF: 0.581 AC: 37567 AN: 64604

Other (OTH) AF: 0.428 AC: 830 AN: 1938

Alfa AF: 0.467 Hom.: 2305

Bravo AF: 0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.86
PhyloP100		-0.38
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: rs4657181; hg19: chr1-162255385;