1-162143120-C-G

Variant names:

• chr1-162143120-C-G
• rs16857031
• NM_014697.3:c.106-11285C>G

Variant summary

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

The NM_014697.3(NOS1AP):​c.106-11285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,624 control chromosomes in the GnomAD database, including 2,773 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 0.18 (2773 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• Publications: 40 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)

LOC105371475 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-11285C>G		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-11285C>G		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.487-9994G>C		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.486+25162G>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-11285C>G		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-11285C>G		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-11285C>G		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26866 AN: 151502 Hom.: 2766 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.177 AC: 26893 AN: 151624 Hom.: 2773 Cov.: 31 AF XY: 0.172 AC XY: 12740 AN XY: 74044

African (AFR) AF: 0.294 AC: 12133 AN: 41278

American (AMR) AF: 0.126 AC: 1923 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3468

East Asian (EAS) AF: 0.187 AC: 954 AN: 5104

South Asian (SAS) AF: 0.0895 AC: 429 AN: 4794

European-Finnish (FIN) AF: 0.0864 AC: 908 AN: 10506

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.140 AC: 9508 AN: 67936

Other (OTH) AF: 0.167 AC: 351 AN: 2100

Alfa AF: 0.147 Hom.: 955

Bravo AF: 0.186

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.64
PhyloP100		0.70
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: rs16857031; hg19: chr1-162112910;