chr1-162238724-G-A

Variant names:

• chr1-162238724-G-A
• rs10918951
• NM_014697.3:c.178-48620G>A

Variant summary

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

The NM_014697.3(NOS1AP):​c.178-48620G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,092 control chromosomes in the GnomAD database, including 828 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 0.085 (828 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 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.178-48620G>A		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.178-48620G>A		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.178-48620G>A		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.178-48620G>A		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.178-48620G>A		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12946 AN: 151974 Hom.: 825 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0846

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

GnomAD4 genome AF: 0.0853 AC: 12972 AN: 152092 Hom.: 828 Cov.: 33 AF XY: 0.0819 AC XY: 6090 AN XY: 74362

African (AFR) AF: 0.186 AC: 7730 AN: 41454

American (AMR) AF: 0.0551 AC: 843 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 329 AN: 3466

East Asian (EAS) AF: 0.00657 AC: 34 AN: 5178

South Asian (SAS) AF: 0.0525 AC: 253 AN: 4818

European-Finnish (FIN) AF: 0.0165 AC: 174 AN: 10574

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0495 AC: 3366 AN: 67996

Other (OTH) AF: 0.0861 AC: 182 AN: 2114

Alfa AF: 0.0814 Hom.: 118

Bravo AF: 0.0923

Asia WGS AF: 0.0420 AC: 147 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.33
PhyloP100		0.49
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: rs10918951; hg19: chr1-162208514;