rs530465271

Variant names:

• chr1-162287694-A-AC
• rs530465271
• NM_014697.3:c.270+264dupC

Your query was ambiguous. Multiple possible variants found:

• chr1-162287694-A-AC
• chr1-162287694-A-ACC
• chr1-162287694-A-ACCC
• chr1-162287694-A-ACCCC
• chr1-162287694-A-ACCCCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014697.3(NOS1AP):​c.270+264dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 150,726 control chromosomes in the GnomAD database, including 251 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.053 (251 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 1-162287694-A-AC is Benign according to our data. Variant chr1-162287694-A-AC is described in ClinVar as [Benign]. Clinvar id is 1280719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.270+264dupC		intron_variant	Intron 3 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.270+264dupC		intron_variant	Intron 3 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.270+258_270+259insC		intron_variant	Intron 3 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.270+258_270+259insC		intron_variant	Intron 3 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.270+258_270+259insC		intron_variant	Intron 3 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8048 AN: 150614 Hom.: 252 Cov.: 31

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.0761

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0581

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0590

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

GnomAD4 genome AF: 0.0534 AC: 8055 AN: 150726 Hom.: 251 Cov.: 31 AF XY: 0.0522 AC XY: 3843 AN XY: 73558

African (AFR) AF: 0.0407 AC: 1672 AN: 41088

American (AMR) AF: 0.0454 AC: 688 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 394 AN: 3436

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5152

South Asian (SAS) AF: 0.0765 AC: 361 AN: 4722

European-Finnish (FIN) AF: 0.0348 AC: 361 AN: 10376

Middle Eastern (MID) AF: 0.0625 AC: 18 AN: 288

European-Non Finnish (NFE) AF: 0.0636 AC: 4292 AN: 67536

Other (OTH) AF: 0.0584 AC: 122 AN: 2090

Alfa AF: 0.0133 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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: rs530465271; hg19: chr1-162257484; COSMIC: COSV62639498;