1-162287694-A-AC

Position:

• chr1-162287694-A-AC

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.270+264dupC		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.270+264dupC		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.270+264dupC		intron_variant		1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.270+264dupC		intron_variant		1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.270+264dupC		intron_variant		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

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0636

Gnomad4 OTH AF: 0.0584

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs530465271; hg19: chr1-162257484;