chr1-162351502-C-A

Variant names:

• chr1-162351502-C-A
• rs429414
• NM_014697.3:c.596-3685C>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.596-3685C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 151,854 control chromosomes in the GnomAD database, including 75,248 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 1.0 (75248 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 1 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 = 0.994 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.596-3685C>A		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.581-3685C>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.596-3685C>A		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.581-3685C>A		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.581-3685C>A		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151057 AN: 151736 Hom.: 75195 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

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

GnomAD4 genome AF: 0.995 AC: 151169 AN: 151854 Hom.: 75248 Cov.: 31 AF XY: 0.996 AC XY: 73885 AN XY: 74216

African (AFR) AF: 0.984 AC: 40742 AN: 41408

American (AMR) AF: 0.999 AC: 15264 AN: 15276

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3466 AN: 3466

East Asian (EAS) AF: 1.00 AC: 5150 AN: 5152

South Asian (SAS) AF: 1.00 AC: 4763 AN: 4764

European-Finnish (FIN) AF: 1.00 AC: 10608 AN: 10608

Middle Eastern (MID) AF: 1.00 AC: 292 AN: 292

European-Non Finnish (NFE) AF: 1.00 AC: 67869 AN: 67870

Other (OTH) AF: 0.999 AC: 2107 AN: 2110

Alfa AF: 0.997 Hom.: 9210

Bravo AF: 0.995

Asia WGS AF: 0.994 AC: 3457 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	0.41
DANN	Benign	0.78
PhyloP100		-0.82
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: rs429414; hg19: chr1-162321292;