chr1-162225948-T-G

Variant names:

• chr1-162225948-T-G
• rs4657175
• NM_014697.3:c.178-61396T>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.178-61396T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,180 control chromosomes in the GnomAD database, including 5,752 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 0.27 (5752 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-61396T>G		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-61396T>G		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.178-61396T>G		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-61396T>G		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-61396T>G		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41116 AN: 152062 Hom.: 5752 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.270 AC: 41132 AN: 152180 Hom.: 5752 Cov.: 33 AF XY: 0.278 AC XY: 20655 AN XY: 74402

African (AFR) AF: 0.308 AC: 12780 AN: 41524

American (AMR) AF: 0.285 AC: 4354 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2040 AN: 5184

South Asian (SAS) AF: 0.349 AC: 1684 AN: 4824

European-Finnish (FIN) AF: 0.307 AC: 3255 AN: 10586

Middle Eastern (MID) AF: 0.217 AC: 63 AN: 290

European-Non Finnish (NFE) AF: 0.226 AC: 15354 AN: 67982

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.235 Hom.: 12402

Bravo AF: 0.267

Asia WGS AF: 0.346 AC: 1200 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	3.9
DANN	Benign	0.64
PhyloP100		0.57
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: rs4657175; hg19: chr1-162195738;