rs17468951

Positions:

• chr1-162361229-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.939+4093A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,976 control chromosomes in the GnomAD database, including 8,749 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 0.33 (8749 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.939+4093A>G		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.924+4093A>G		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.939+4093A>G		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.924+4093A>G		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.1037+305A>G		intron_variant, NMD_transcript_variant		1		ENSP00000396713
NOS1AP	ENST00000464284.1	c.-94+305A>G		intron_variant		4		ENSP00000435711

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50810 AN: 151858 Hom.: 8750 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.334 AC: 50821 AN: 151976 Hom.: 8749 Cov.: 32 AF XY: 0.330 AC XY: 24495 AN XY: 74258

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.380

Alfa AF: 0.344 Hom.: 1115

Bravo AF: 0.333

Asia WGS AF: 0.283 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.78

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: rs17468951; hg19: chr1-162331019;