1-162360400-C-T

Variant names:

• chr1-162360400-C-T
• rs1504430
• NM_014697.3:c.939+3264C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_014697.3(NOS1AP):​c.939+3264C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 164,744 control chromosomes in the GnomAD database, including 8,394 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 0.29 (7645 hom., cov: 32)
  • Exomes 𝑓: 0.32 (749 hom.)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• 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)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 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.939+3264C>T		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.924+3264C>T		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.939+3264C>T		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.924+3264C>T		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.925-412C>T		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44663 AN: 151996 Hom.: 7638 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.322 AC: 4069 AN: 12630 Hom.: 749 AF XY: 0.312 AC XY: 2109 AN XY: 6764

African (AFR) AF: 0.119 AC: 38 AN: 318

American (AMR) AF: 0.391 AC: 538 AN: 1376

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 66 AN: 268

East Asian (EAS) AF: 0.504 AC: 234 AN: 464

South Asian (SAS) AF: 0.192 AC: 263 AN: 1372

European-Finnish (FIN) AF: 0.372 AC: 125 AN: 336

Middle Eastern (MID) AF: 0.182 AC: 8 AN: 44

European-Non Finnish (NFE) AF: 0.331 AC: 2587 AN: 7812

Other (OTH) AF: 0.328 AC: 210 AN: 640

GnomAD4 genome AF: 0.294 AC: 44670 AN: 152114 Hom.: 7645 Cov.: 32 AF XY: 0.297 AC XY: 22099 AN XY: 74332

African (AFR) AF: 0.121 AC: 5015 AN: 41532

American (AMR) AF: 0.378 AC: 5777 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.504 AC: 2597 AN: 5156

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4810

European-Finnish (FIN) AF: 0.405 AC: 4279 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24029 AN: 67984

Other (OTH) AF: 0.298 AC: 630 AN: 2114

Alfa AF: 0.334 Hom.: 3063

Bravo AF: 0.289

Asia WGS AF: 0.333 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		0.21
PromoterAI		0.0029	Neutral
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: rs1504430; hg19: chr1-162330190;