NM_014697.3:c.177+6020G>A

Variant names:

• chr1-162160496-G-A
• rs12026452
• NM_014697.3:c.177+6020G>A

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+6020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,164 control chromosomes in the GnomAD database, including 2,891 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 0.16 (2891 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• 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)

LOC105371475 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+6020G>A		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+6020G>A		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+6020G>A		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+6020G>A		intron_variant	Intron 2 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.438+7786C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24275 AN: 152046 Hom.: 2892 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.160 AC: 24272 AN: 152164 Hom.: 2891 Cov.: 32 AF XY: 0.172 AC XY: 12759 AN XY: 74358

African (AFR) AF: 0.0411 AC: 1708 AN: 41544

American (AMR) AF: 0.212 AC: 3235 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2861 AN: 5164

South Asian (SAS) AF: 0.363 AC: 1749 AN: 4818

European-Finnish (FIN) AF: 0.273 AC: 2884 AN: 10556

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10550 AN: 68004

Other (OTH) AF: 0.173 AC: 365 AN: 2110

Alfa AF: 0.151 Hom.: 2110

Bravo AF: 0.146

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.66
DANN	Benign	0.70
PhyloP100		-1.2
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: rs12026452; hg19: chr1-162130286;