rs905721

chr1-162365262-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000493151.1(NOS1AP):c.-88C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,507,558 control chromosomes in the GnomAD database, including 100,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8491 hom., cov: 33)
  • Exomes 𝑓: 0.36 (92358 hom.)
• Consequence: NOS1AP ENST00000493151.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0430

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-162365262-C-T is Benign according to our data. Variant chr1-162365262-C-T is described in ClinVar as [Benign]. Clinvar id is 1238681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.940-142C>T		intron_variant		ENST00000361897.10
NOS1AP	NM_001126060.2	c.-88C>T		5_prime_UTR_variant	1/2
NOS1AP	NM_001164757.2	c.925-142C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.940-142C>T		intron_variant		1	NM_014697.3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47134 AN: 152010 Hom.: 8483 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.364 AC: 493390 AN: 1355430 Hom.: 92358 Cov.: 58 AF XY: 0.361 AC XY: 239382 AN XY: 662908

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.310 AC: 47141 AN: 152128 Hom.: 8491 Cov.: 33 AF XY: 0.315 AC XY: 23408 AN XY: 74350

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.319

Alfa AF: 0.341 Hom.: 1204

Bravo AF: 0.303

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.6
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: rs905721; hg19: chr1-162335052; COSMIC: COSV62641562; COSMIC: COSV62641562;