1-162119528-G-A

Variant names:

• chr1-162119528-G-A
• rs76662883
• NM_014697.3:c.106-34877G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014697.3(NOS1AP):​c.106-34877G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00869 in 152,278 control chromosomes in the GnomAD database, including 12 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 0.0087 (12 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 3 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)

LOC105371475 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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.106-34877G>A		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.106-34877G>A		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.106-34877G>A		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.106-34877G>A		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.106-34877G>A		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.00870 AC: 1324 AN: 152160 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.00860

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

GnomAD4 genome AF: 0.00869 AC: 1324 AN: 152278 Hom.: 12 Cov.: 32 AF XY: 0.00810 AC XY: 603 AN XY: 74450

African (AFR) AF: 0.00224 AC: 93 AN: 41562

American (AMR) AF: 0.00373 AC: 57 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10614

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0143 AC: 974 AN: 68016

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00640 Hom.: 0

Bravo AF: 0.00814

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.82
PhyloP100		0.61
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: rs76662883; hg19: chr1-162089318;