rs12742393

Variant names:

• chr1-162254796-A-C
• rs12742393
• NM_014697.3:c.178-32548A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-162254796-A-C
• chr1-162254796-A-T

Variant summary

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

The NM_014697.3(NOS1AP):​c.178-32548A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,092 control chromosomes in the GnomAD database, including 16,475 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 0.44 (16475 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 33 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 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.178-32548A>C		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.178-32548A>C		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.178-32548A>C		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.178-32548A>C		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.178-32548A>C		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66534 AN: 151974 Hom.: 16468 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.438 AC: 66562 AN: 152092 Hom.: 16475 Cov.: 32 AF XY: 0.432 AC XY: 32148 AN XY: 74332

African (AFR) AF: 0.216 AC: 8965 AN: 41504

American (AMR) AF: 0.442 AC: 6747 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1506 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5176

South Asian (SAS) AF: 0.378 AC: 1824 AN: 4822

European-Finnish (FIN) AF: 0.536 AC: 5663 AN: 10562

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39243 AN: 67970

Other (OTH) AF: 0.461 AC: 973 AN: 2110

Alfa AF: 0.519 Hom.: 58405

Bravo AF: 0.423

Asia WGS AF: 0.315 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		0.21
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: rs12742393; hg19: chr1-162224586;