1-162285496-T-G

Variant names:

• chr1-162285496-T-G
• rs6680461
• NM_014697.3:c.178-1848T>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.178-1848T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,026 control chromosomes in the GnomAD database, including 6,759 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 0.29 (6759 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• 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 (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-1848T>G		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-1848T>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.178-1848T>G		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-1848T>G		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-1848T>G		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43831 AN: 151908 Hom.: 6737 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.289 AC: 43906 AN: 152026 Hom.: 6759 Cov.: 32 AF XY: 0.296 AC XY: 22011 AN XY: 74318

African (AFR) AF: 0.304 AC: 12612 AN: 41470

American (AMR) AF: 0.356 AC: 5432 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3472

East Asian (EAS) AF: 0.593 AC: 3064 AN: 5168

South Asian (SAS) AF: 0.366 AC: 1757 AN: 4806

European-Finnish (FIN) AF: 0.271 AC: 2859 AN: 10568

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16078 AN: 67948

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.127 Hom.: 197

Bravo AF: 0.296

Asia WGS AF: 0.459 AC: 1598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.82
PhyloP100		-0.16
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: rs6680461; hg19: chr1-162255286;