1-162248149-T-G

Position:

• chr1-162248149-T-G

Variant summary

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

The NM_014697.3(NOS1AP):​c.178-39195T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 151,898 control chromosomes in the GnomAD database, including 49,553 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 0.81 (49553 hom., cov: 29)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-39195T>G		intron_variant		ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-39195T>G		intron_variant			NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.178-39195T>G		intron_variant		1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-39195T>G		intron_variant		1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-39195T>G		intron_variant		1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122441 AN: 151780 Hom.: 49523 Cov.: 29

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.807 AC: 122520 AN: 151898 Hom.: 49553 Cov.: 29 AF XY: 0.806 AC XY: 59806 AN XY: 74200

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.816

Alfa AF: 0.792 Hom.: 2521

Bravo AF: 0.799

Asia WGS AF: 0.757 AC: 2628 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.35

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: rs4657179; hg19: chr1-162217939;