rs1508262

Variant names:

• chr1-162309428-G-A
• rs1508262
• NM_014697.3:c.344+8722G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-162309428-G-A
• chr1-162309428-G-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.344+8722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,086 control chromosomes in the GnomAD database, including 23,917 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 0.56 (23917 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.344+8722G>A		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.329+8722G>A		intron	N/A	NP_001158229.1	O75052-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.344+8722G>A		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.329+8722G>A		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.329+8722G>A		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84936 AN: 151966 Hom.: 23882 Cov.: 33

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.559 AC: 85020 AN: 152086 Hom.: 23917 Cov.: 33 AF XY: 0.563 AC XY: 41838 AN XY: 74338

African (AFR) AF: 0.555 AC: 23010 AN: 41488

American (AMR) AF: 0.582 AC: 8900 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1588 AN: 3466

East Asian (EAS) AF: 0.597 AC: 3084 AN: 5168

South Asian (SAS) AF: 0.597 AC: 2881 AN: 4828

European-Finnish (FIN) AF: 0.596 AC: 6300 AN: 10566

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37355 AN: 67964

Other (OTH) AF: 0.548 AC: 1157 AN: 2112

Alfa AF: 0.556 Hom.: 2945

Bravo AF: 0.555

Asia WGS AF: 0.602 AC: 2092 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.93
DANN	Benign	0.55
PhyloP100		-1.1
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: rs1508262; hg19: chr1-162279218;