1-162332789-C-T

Variant names:

• chr1-162332789-C-T
• rs116374043
• NM_014697.3:c.345-228C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014697.3(NOS1AP):​c.345-228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 152,294 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.014 (25 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.696
• 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=-0.83).
• BP6: Variant 1-162332789-C-T is Benign according to our data. Variant chr1-162332789-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316249.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0137 (2083/152294) while in subpopulation NFE AF = 0.0199 (1354/68022). AF 95% confidence interval is 0.019. There are 25 homozygotes in GnomAd4. There are 1089 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.345-228C>T		intron_variant	Intron 4 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.330-228C>T		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.345-228C>T		intron_variant	Intron 4 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.330-228C>T		intron_variant	Intron 4 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.330-228C>T		intron_variant	Intron 4 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2083 AN: 152176 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0149

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

GnomAD4 genome AF: 0.0137 AC: 2083 AN: 152294 Hom.: 25 Cov.: 32 AF XY: 0.0146 AC XY: 1089 AN XY: 74476

African (AFR) AF: 0.00260 AC: 108 AN: 41562

American (AMR) AF: 0.0155 AC: 238 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4820

European-Finnish (FIN) AF: 0.0204 AC: 216 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0199 AC: 1354 AN: 68022

Other (OTH) AF: 0.0147 AC: 31 AN: 2106

Alfa AF: 0.0186 Hom.: 40

Bravo AF: 0.0126

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 15, 2020

GeneDx

Significance: Likely 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	-0.83
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		0.70
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: rs116374043; hg19: chr1-162302579;