rs16859092

Positions:

• chr1-162254760-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.178-32584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,278 control chromosomes in the GnomAD database, including 415 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 0.064 (415 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.178-32584T>C		intron_variant		ENST00000361897.10
NOS1AP	NM_001164757.2	c.178-32584T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.178-32584T>C		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.178-32584T>C		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.178-32584T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9797 AN: 152160 Hom.: 414 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0697

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

GnomAD4 genome AF: 0.0645 AC: 9817 AN: 152278 Hom.: 415 Cov.: 33 AF XY: 0.0612 AC XY: 4558 AN XY: 74452

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0951

Gnomad4 EAS AF: 0.00655

Gnomad4 SAS AF: 0.0524

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0517 Hom.: 296

Bravo AF: 0.0684

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.84

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: rs16859092; hg19: chr1-162224550;