1-162267300-C-T

Position:

• chr1-162267300-C-T

Variant summary

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

The NM_014697.3(NOS1AP):​c.178-20044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,954 control chromosomes in the GnomAD database, including 5,881 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 0.27 (5881 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-20044C>T		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-20044C>T		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.178-20044C>T		intron_variant		1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-20044C>T		intron_variant		1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-20044C>T		intron_variant		1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41396 AN: 151838 Hom.: 5862 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.273 AC: 41458 AN: 151954 Hom.: 5881 Cov.: 31 AF XY: 0.280 AC XY: 20817 AN XY: 74246

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.274

Alfa AF: 0.141 Hom.: 261

Bravo AF: 0.275

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.63

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: rs10800397; hg19: chr1-162237090;