rs12122048

chr1-162361618-G-Achr1-162361618-G-C

Variant summary

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

The NM_014697.3(NOS1AP):c.940-3786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,020 control chromosomes in the GnomAD database, including 9,129 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 0.34 (9129 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.940-3786G>A		intron_variant		ENST00000361897.10
NOS1AP	NM_001164757.2	c.925-3786G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.940-3786G>A		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.925-3786G>A		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.1037+694G>A		intron_variant, NMD_transcript_variant		1
NOS1AP	ENST00000464284.1	c.-94+694G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52005 AN: 151904 Hom.: 9119 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.342 AC: 52042 AN: 152020 Hom.: 9129 Cov.: 33 AF XY: 0.338 AC XY: 25133 AN XY: 74302

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.386

Alfa AF: 0.362 Hom.: 17484

Bravo AF: 0.340

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.77
Dann	Benign	0.35

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: rs12122048; hg19: chr1-162331408;