1-162287701-T-C

Variant names:

• chr1-162287701-T-C
• rs59636124
• NM_014697.3:c.270+265T>C

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.270+265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 151,338 control chromosomes in the GnomAD database, including 501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.076 (501 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-162287701-T-C is Benign according to our data. Variant chr1-162287701-T-C is described in ClinVar as [Benign]. Clinvar id is 1288060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.270+265T>C		intron_variant	Intron 3 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.270+265T>C		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+265T>C		intron_variant	Intron 3 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.270+265T>C		intron_variant	Intron 3 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.270+265T>C		intron_variant	Intron 3 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11423 AN: 151218 Hom.: 501 Cov.: 32

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0845

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

GnomAD4 genome AF: 0.0756 AC: 11442 AN: 151338 Hom.: 501 Cov.: 32 AF XY: 0.0737 AC XY: 5442 AN XY: 73874

African (AFR) AF: 0.0630 AC: 2601 AN: 41308

American (AMR) AF: 0.0691 AC: 1050 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3462

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5166

South Asian (SAS) AF: 0.0838 AC: 400 AN: 4774

European-Finnish (FIN) AF: 0.0544 AC: 567 AN: 10416

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0867 AC: 5871 AN: 67718

Other (OTH) AF: 0.0836 AC: 176 AN: 2106

Alfa AF: 0.0412 Hom.: 52

Bravo AF: 0.0781

Asia WGS AF: 0.0390 AC: 140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 04, 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	-0.85
CADD	Benign	0.13
DANN	Benign	0.71
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: rs59636124; hg19: chr1-162257491;