rs16859092

Variant names:

• chr1-162254760-T-C
• rs16859092
• NM_014697.3:c.178-32584T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.178-32584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,278 control chromosomes in the GnomAD database, including 415 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 0.064 (415 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-32584T>C		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-32584T>C		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.178-32584T>C		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-32584T>C		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-32584T>C		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9797 AN: 152160 Hom.: 414 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0697

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

GnomAD4 genome AF: 0.0645 AC: 9817 AN: 152278 Hom.: 415 Cov.: 33 AF XY: 0.0612 AC XY: 4558 AN XY: 74452

African (AFR) AF: 0.115 AC: 4762 AN: 41536

American (AMR) AF: 0.0465 AC: 711 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.00655 AC: 34 AN: 5188

South Asian (SAS) AF: 0.0524 AC: 253 AN: 4824

European-Finnish (FIN) AF: 0.0164 AC: 174 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0492 AC: 3347 AN: 68026

Other (OTH) AF: 0.0714 AC: 151 AN: 2116

Alfa AF: 0.0539 Hom.: 403

Bravo AF: 0.0684

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.84
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: rs16859092; hg19: chr1-162224550;