1-162332775-G-A

Variant names:

• chr1-162332775-G-A
• rs56178763
• NM_014697.3:c.345-242G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014697.3(NOS1AP):​c.345-242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 152,266 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (276 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.310
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-162332775-G-A is Benign according to our data. Variant chr1-162332775-G-A is described in ClinVar as [Benign]. Clinvar id is 1230924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.345-242G>A		intron_variant	Intron 4 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.330-242G>A		intron_variant	Intron 4 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.345-242G>A		intron_variant	Intron 4 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.330-242G>A		intron_variant	Intron 4 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.330-242G>A		intron_variant	Intron 4 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7777 AN: 152148 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0511 AC: 7777 AN: 152266 Hom.: 276 Cov.: 32 AF XY: 0.0496 AC XY: 3690 AN XY: 74456

African (AFR) AF: 0.0137 AC: 569 AN: 41566

American (AMR) AF: 0.0535 AC: 819 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4818

European-Finnish (FIN) AF: 0.0504 AC: 534 AN: 10604

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0785 AC: 5342 AN: 68008

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0635 Hom.: 42

Bravo AF: 0.0515

Asia WGS AF: 0.00779 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.53
PhyloP100		-0.31
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: rs56178763; hg19: chr1-162302565;