rs12742393

Positions:

• chr1-162254796-A-C
• chr1-162254796-A-T

Variant summary

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

The NM_014697.3(NOS1AP):​c.178-32548A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,092 control chromosomes in the GnomAD database, including 16,475 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 0.44 (16475 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-32548A>C		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-32548A>C		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.178-32548A>C		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.178-32548A>C		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.178-32548A>C		intron_variant, NMD_transcript_variant		1		ENSP00000396713

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66534 AN: 151974 Hom.: 16468 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.438 AC: 66562 AN: 152092 Hom.: 16475 Cov.: 32 AF XY: 0.432 AC XY: 32148 AN XY: 74332

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.461

Alfa AF: 0.543 Hom.: 36806

Bravo AF: 0.423

Asia WGS AF: 0.315 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
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: rs12742393; hg19: chr1-162224586;