chr1-162154007-A-G

Variant names:

• chr1-162154007-A-G
• rs4656355
• NM_014697.3:c.106-398A>G

Variant summary

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

The NM_014697.3(NOS1AP):​c.106-398A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 150,356 control chromosomes in the GnomAD database, including 18,740 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 0.45 (18740 hom., cov: 26)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 10 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)

ENSG00000285636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.106-398A>G		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.106-398A>G		intron	N/A	NP_001158229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.106-398A>G		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.106-398A>G		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.106-398A>G		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 67700 AN: 150244 Hom.: 18729 Cov.: 26

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.555

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.450 AC: 67721 AN: 150356 Hom.: 18740 Cov.: 26 AF XY: 0.449 AC XY: 32917 AN XY: 73324

African (AFR) AF: 0.132 AC: 5415 AN: 40970

American (AMR) AF: 0.565 AC: 8556 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1673 AN: 3458

East Asian (EAS) AF: 0.242 AC: 1243 AN: 5138

South Asian (SAS) AF: 0.332 AC: 1578 AN: 4752

European-Finnish (FIN) AF: 0.578 AC: 5796 AN: 10028

Middle Eastern (MID) AF: 0.569 AC: 164 AN: 288

European-Non Finnish (NFE) AF: 0.618 AC: 41745 AN: 67598

Other (OTH) AF: 0.496 AC: 1033 AN: 2084

Alfa AF: 0.313 Hom.: 2741

Bravo AF: 0.442

Asia WGS AF: 0.303 AC: 1052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.9
DANN	Benign	0.86
PhyloP100		-0.10
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: rs4656355; hg19: chr1-162123797;