NM_014697.3:c.106-24894G>A

Variant names:

• chr1-162129511-G-A
• rs1572495
• NM_014697.3:c.106-24894G>A

Variant summary

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

The NM_014697.3(NOS1AP):​c.106-24894G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,088 control chromosomes in the GnomAD database, including 8,083 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 0.23 (8083 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-24894G>A		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-24894G>A		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066699.1	n.487-15609C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-24894G>A		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-24894G>A		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-24894G>A		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35574 AN: 151970 Hom.: 8065 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.234 AC: 35635 AN: 152088 Hom.: 8083 Cov.: 32 AF XY: 0.228 AC XY: 16949 AN XY: 74346

African (AFR) AF: 0.598 AC: 24778 AN: 41434

American (AMR) AF: 0.118 AC: 1808 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3472

East Asian (EAS) AF: 0.177 AC: 918 AN: 5182

South Asian (SAS) AF: 0.0734 AC: 354 AN: 4826

European-Finnish (FIN) AF: 0.0774 AC: 820 AN: 10594

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0909 AC: 6177 AN: 67988

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.126 Hom.: 11069

Bravo AF: 0.253

Asia WGS AF: 0.141 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.80
PhyloP100		-1.2
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: rs1572495; hg19: chr1-162099301;