1-162356033-C-T

Variant names:

• chr1-162356033-C-T
• rs386231
• NM_014697.3:c.762+680C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014697.3(NOS1AP):​c.762+680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,078 control chromosomes in the GnomAD database, including 36,112 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 0.69 (36112 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 13 publications found

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]

NOS1AP Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 22

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.762+680C>T		intron_variant	Intron 7 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.747+680C>T		intron_variant	Intron 7 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.762+680C>T		intron_variant	Intron 7 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.747+680C>T		intron_variant	Intron 7 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.747+680C>T		intron_variant	Intron 7 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104310 AN: 151960 Hom.: 36080 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.686 AC: 104387 AN: 152078 Hom.: 36112 Cov.: 32 AF XY: 0.687 AC XY: 51041 AN XY: 74318

African (AFR) AF: 0.592 AC: 24542 AN: 41454

American (AMR) AF: 0.746 AC: 11404 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2730 AN: 3468

East Asian (EAS) AF: 0.731 AC: 3783 AN: 5176

South Asian (SAS) AF: 0.706 AC: 3405 AN: 4824

European-Finnish (FIN) AF: 0.679 AC: 7181 AN: 10578

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.720 AC: 48935 AN: 67986

Other (OTH) AF: 0.718 AC: 1517 AN: 2112

Alfa AF: 0.695 Hom.: 13085

Bravo AF: 0.688

Asia WGS AF: 0.691 AC: 2405 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	2.3
DANN	Benign	0.34
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs386231; hg19: chr1-162325823;