1-162360400-C-T

Position:

• chr1-162360400-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.939+3264C>T		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.924+3264C>T		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.939+3264C>T		intron_variant		1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.924+3264C>T		intron_variant		1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.925-412C>T		intron_variant		1		ENSP00000396713.3

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

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.328

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.298

Alfa AF: 0.332 Hom.: 1783

Bravo AF: 0.289

Asia WGS AF: 0.333 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	17
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs1504430; hg19: chr1-162330190;