1-162349539-T-C

Variant names:

• chr1-162349539-T-C
• rs347271
• NM_014697.3:c.595+5563T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.595+5563T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,214 control chromosomes in the GnomAD database, including 64,416 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (64416 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.595+5563T>C		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.580+5563T>C		intron	N/A	NP_001158229.1	O75052-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.595+5563T>C		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.580+5563T>C		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.580+5563T>C		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139392 AN: 152096 Hom.: 64373 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.916 AC: 139492 AN: 152214 Hom.: 64416 Cov.: 32 AF XY: 0.919 AC XY: 68445 AN XY: 74450

African (AFR) AF: 0.791 AC: 32822 AN: 41474

American (AMR) AF: 0.951 AC: 14557 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3300 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5168

South Asian (SAS) AF: 0.934 AC: 4502 AN: 4820

European-Finnish (FIN) AF: 0.983 AC: 10437 AN: 10614

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.965 AC: 65674 AN: 68038

Other (OTH) AF: 0.939 AC: 1984 AN: 2112

Alfa AF: 0.954 Hom.: 128017

Bravo AF: 0.911

Asia WGS AF: 0.960 AC: 3339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.74
PhyloP100		-0.33
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: rs347271; hg19: chr1-162319329;