1-162091475-T-C

Position:

• chr1-162091475-T-C

Variant summary

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

The NM_014697.3(NOS1AP):​c.105+21193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,080 control chromosomes in the GnomAD database, including 21,738 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 0.51 (21738 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.105+21193T>C		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.105+21193T>C		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.105+21193T>C		intron_variant		1	NM_014697.3	ENSP00000355133
NOS1AP	ENST00000530878.5	c.105+21193T>C		intron_variant		1		ENSP00000431586	P1
NOS1AP	ENST00000430120.3	c.105+21193T>C		intron_variant, NMD_transcript_variant		1		ENSP00000396713

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77105 AN: 151964 Hom.: 21725 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.507 AC: 77138 AN: 152080 Hom.: 21738 Cov.: 32 AF XY: 0.507 AC XY: 37677 AN XY: 74342

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.527

Alfa AF: 0.595 Hom.: 13767

Bravo AF: 0.499

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.80

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: rs4657140; hg19: chr1-162061265;