1-162349539-T-C

Position:

• chr1-162349539-T-C

Variant summary

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

The NM_014697.3(NOS1AP):​c.595+5563T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,214 control chromosomes in the GnomAD database, including 64,416 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 0.92 (64416 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.595+5563T>C		intron_variant		ENST00000361897.10
NOS1AP	NM_001164757.2	c.580+5563T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.595+5563T>C		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.580+5563T>C		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.580+5563T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139392 AN: 152096 Hom.: 64373 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.916 AC: 139492 AN: 152214 Hom.: 64416 Cov.: 32 AF XY: 0.919 AC XY: 68445 AN XY: 74450

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.939

Alfa AF: 0.958 Hom.: 90764

Bravo AF: 0.911

Asia WGS AF: 0.960 AC: 3339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.74

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: rs347271; hg19: chr1-162319329;