1-162115895-G-T

Variant names:

• chr1-162115895-G-T
• rs10494366
• NM_014697.3:c.106-38510G>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.106-38510G>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 152,000 control chromosomes in the GnomAD database, including 23,424 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 (23424 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 119 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.106-38510G>T		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.106-38510G>T		intron	N/A	NP_001158229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.106-38510G>T		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.106-38510G>T		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.106-38510G>T		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82143 AN: 151882 Hom.: 23407 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.573

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: 82191 AN: 152000 Hom.: 23424 Cov.: 31 AF XY: 0.539 AC XY: 40068 AN XY: 74306

African (AFR) AF: 0.382 AC: 15818 AN: 41434

American (AMR) AF: 0.591 AC: 9037 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1652 AN: 5166

South Asian (SAS) AF: 0.358 AC: 1725 AN: 4824

European-Finnish (FIN) AF: 0.633 AC: 6681 AN: 10552

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.639 AC: 43425 AN: 67964

Other (OTH) AF: 0.555 AC: 1172 AN: 2110

Alfa AF: 0.603 Hom.: 112285

Bravo AF: 0.538

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.67
PhyloP100		-1.7
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: rs10494366; hg19: chr1-162085685;