rs2341744

chr1-162299232-G-Achr1-162299232-G-T

Variant summary

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

The NM_014697.3(NOS1AP):c.271-1401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,924 control chromosomes in the GnomAD database, including 17,557 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 0.48 (17557 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.271-1401G>A		intron_variant		ENST00000361897.10
NOS1AP	NM_001164757.2	c.271-1416G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.271-1401G>A		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.271-1416G>A		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.271-1416G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72407 AN: 151806 Hom.: 17549 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.477 AC: 72440 AN: 151924 Hom.: 17557 Cov.: 31 AF XY: 0.473 AC XY: 35103 AN XY: 74248

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.494

Alfa AF: 0.480 Hom.: 2904

Bravo AF: 0.477

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.64

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: rs2341744; hg19: chr1-162269022;