chr1-162114199-C-G

Variant names:

• chr1-162114199-C-G
• rs10494365
• NM_014697.3:c.106-40206C>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.106-40206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,942 control chromosomes in the GnomAD database, including 1,520 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 0.12 (1520 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 6 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.106-40206C>G		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.106-40206C>G		intron	N/A	NP_001158229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.106-40206C>G		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.106-40206C>G		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.106-40206C>G		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17596 AN: 151826 Hom.: 1523 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.116 AC: 17580 AN: 151942 Hom.: 1520 Cov.: 32 AF XY: 0.121 AC XY: 9011 AN XY: 74224

African (AFR) AF: 0.0258 AC: 1071 AN: 41460

American (AMR) AF: 0.119 AC: 1821 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3466

East Asian (EAS) AF: 0.330 AC: 1700 AN: 5144

South Asian (SAS) AF: 0.312 AC: 1500 AN: 4810

European-Finnish (FIN) AF: 0.165 AC: 1738 AN: 10516

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8859 AN: 67984

Other (OTH) AF: 0.111 AC: 234 AN: 2104

Alfa AF: 0.0548 Hom.: 63

Bravo AF: 0.104

Asia WGS AF: 0.296 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		-0.082
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: rs10494365; hg19: chr1-162083989;