1-162287243-C-G

Position:

• chr1-162287243-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014697.3(NOS1AP):​c.178-101C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 808,154 control chromosomes in the GnomAD database, including 35,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6745 hom., cov: 32)
  • Exomes 𝑓: 0.28 (28272 hom.)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0950

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-162287243-C-G is Benign according to our data. Variant chr1-162287243-C-G is described in ClinVar as [Benign]. Clinvar id is 1248946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-101C>G		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-101C>G		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.178-101C>G		intron_variant		1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-101C>G		intron_variant		1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-101C>G		intron_variant		1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43726 AN: 151884 Hom.: 6722 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.280 AC: 183644 AN: 656152 Hom.: 28272 AF XY: 0.282 AC XY: 99027 AN XY: 350678

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.288 AC: 43802 AN: 152002 Hom.: 6745 Cov.: 32 AF XY: 0.295 AC XY: 21927 AN XY: 74296

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.291

Alfa AF: 0.260 Hom.: 657

Bravo AF: 0.295

Asia WGS AF: 0.460 AC: 1601 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 16, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.51

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: rs10800405; hg19: chr1-162257033;