rs1963645

Positions:

• chr1-162364200-A-G

Variant summary

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

The NM_001126060.2(NOS1AP):​c.-1150A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 985,208 control chromosomes in the GnomAD database, including 62,388 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 (8801 hom., cov: 32)
  • Exomes 𝑓: 0.36 (53587 hom.)
• Consequence: NOS1AP NM_001126060.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785

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 (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.940-1204A>G		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001126060.2	c.-1150A>G		5_prime_UTR_variant	1/2		NP_001119532.2
NOS1AP	NM_001164757.2	c.925-1204A>G		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.940-1204A>G		intron_variant		1	NM_014697.3	ENSP00000355133.5

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50983 AN: 151958 Hom.: 8800 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.358 AC: 298063 AN: 833128 Hom.: 53587 Cov.: 29 AF XY: 0.358 AC XY: 137653 AN XY: 384724

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.335 AC: 50998 AN: 152080 Hom.: 8801 Cov.: 32 AF XY: 0.330 AC XY: 24570 AN XY: 74368

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.381

Alfa AF: 0.361 Hom.: 13301

Bravo AF: 0.334

Asia WGS AF: 0.281 AC: 980 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	1.2
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: rs1963645; hg19: chr1-162333990;