1-162199478-G-A

Position:

• chr1-162199478-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.177+45002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,168 control chromosomes in the GnomAD database, including 2,885 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 0.17 (2885 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+45002G>A		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.177+45002G>A		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+45002G>A		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.177+45002G>A		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.177+45002G>A		intron_variant, NMD_transcript_variant		1		ENSP00000396713

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25452 AN: 152050 Hom.: 2886 Cov.: 32

Gnomad AFR AF: 0.0343

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.167 AC: 25445 AN: 152168 Hom.: 2885 Cov.: 32 AF XY: 0.178 AC XY: 13213 AN XY: 74386

Gnomad4 AFR AF: 0.0342

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.179

Alfa AF: 0.191 Hom.: 1633

Bravo AF: 0.155

Asia WGS AF: 0.315 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.30

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: rs10918859; hg19: chr1-162169268;