1-162115519-C-T

Variant names:

• chr1-162115519-C-T
• rs1415259
• NM_014697.3:c.106-38886C>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.106-38886C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,922 control chromosomes in the GnomAD database, including 23,418 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 0.54 (23418 hom., cov: 30)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 35 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-38886C>T		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-38886C>T		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066699.1	n.487-1617G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-38886C>T		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-38886C>T		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-38886C>T		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82115 AN: 151804 Hom.: 23401 Cov.: 30

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.541 AC: 82163 AN: 151922 Hom.: 23418 Cov.: 30 AF XY: 0.539 AC XY: 40043 AN XY: 74250

African (AFR) AF: 0.382 AC: 15796 AN: 41390

American (AMR) AF: 0.592 AC: 9040 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1650 AN: 5166

South Asian (SAS) AF: 0.358 AC: 1722 AN: 4814

European-Finnish (FIN) AF: 0.633 AC: 6680 AN: 10546

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43421 AN: 67948

Other (OTH) AF: 0.555 AC: 1169 AN: 2106

Alfa AF: 0.595 Hom.: 70047

Bravo AF: 0.538

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.49
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: rs1415259; hg19: chr1-162085309;