1-162332899-C-T

Variant summary

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

The NM_014697.3(NOS1AP):c.345-118C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 754,940 control chromosomes in the GnomAD database, including 91,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (15721 hom., cov: 32)
  • Exomes 𝑓: 0.49 (75453 hom.)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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=-0.83).
• BP6: Variant 1-162332899-C-T is Benign according to our data. Variant chr1-162332899-C-T is described in ClinVar as [Benign]. Clinvar id is 1293317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1AP	NM_014697.3	c.345-118C>T		intron_variant		ENST00000361897.10
NOS1AP	NM_001164757.2	c.330-118C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1AP	ENST00000361897.10	c.345-118C>T		intron_variant		1	NM_014697.3
NOS1AP	ENST00000530878.5	c.330-118C>T		intron_variant		1		P1
NOS1AP	ENST00000430120.3	c.330-118C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66479 AN: 151878 Hom.: 15720 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.488 AC: 294086 AN: 602944 Hom.: 75453 AF XY: 0.482 AC XY: 157132 AN XY: 325850

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.452

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.437 AC: 66482 AN: 151996 Hom.: 15721 Cov.: 32 AF XY: 0.430 AC XY: 31956 AN XY: 74274

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.467

Alfa AF: 0.490 Hom.: 2334

Bravo AF: 0.433

Asia WGS AF: 0.308 AC: 1073 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	-0.83
Cadd	Benign	4.3
Dann	Benign	0.32

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: rs347307; hg19: chr1-162302689; COSMIC: COSV62635284;