rs11577628

chr1-162349734-A-G

Variant summary

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

The NM_014697.3(NOS1AP):c.596-5453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 152,230 control chromosomes in the GnomAD database, including 608 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 0.076 (608 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.596-5453A>G		intron_variant		ENST00000361897.10
NOS1AP	NM_001164757.2	c.581-5453A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.596-5453A>G		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.581-5453A>G		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.581-5453A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11565 AN: 152112 Hom.: 609 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0606

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.0764

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

GnomAD4 genome AF: 0.0759 AC: 11558 AN: 152230 Hom.: 608 Cov.: 33 AF XY: 0.0793 AC XY: 5903 AN XY: 74432

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.0946

Gnomad4 OTH AF: 0.0761

Alfa AF: 0.0899 Hom.: 700

Bravo AF: 0.0661

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.058
Dann	Benign	0.68

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: rs11577628; hg19: chr1-162319524;