rs4145621

Positions:

• chr1-162248898-C-T

Variant summary

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

The ENST00000361897.10(NOS1AP):​c.178-38446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,886 control chromosomes in the GnomAD database, including 14,615 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 0.40 (14615 hom., cov: 31)
• Consequence: NOS1AP ENST00000361897.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-38446C>T		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-38446C>T		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.178-38446C>T		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.178-38446C>T		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.178-38446C>T		intron_variant, NMD_transcript_variant		1		ENSP00000396713

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60340 AN: 151766 Hom.: 14613 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.397 AC: 60345 AN: 151886 Hom.: 14615 Cov.: 31 AF XY: 0.393 AC XY: 29196 AN XY: 74202

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.412

Alfa AF: 0.500 Hom.: 9663

Bravo AF: 0.379

Asia WGS AF: 0.298 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.69

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: rs4145621; hg19: chr1-162218688;