1-162295024-C-G

Variant names:

• chr1-162295024-C-G
• rs2661818
• NM_014697.3:c.271-5609C>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.271-5609C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,026 control chromosomes in the GnomAD database, including 13,588 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 0.39 (13588 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.271-5609C>G		intron_variant	Intron 3 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.271-5624C>G		intron_variant	Intron 3 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.271-5609C>G		intron_variant	Intron 3 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.271-5624C>G		intron_variant	Intron 3 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.271-5624C>G		intron_variant	Intron 3 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58991 AN: 151906 Hom.: 13589 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.388 AC: 58992 AN: 152026 Hom.: 13588 Cov.: 31 AF XY: 0.384 AC XY: 28530 AN XY: 74314

African (AFR) AF: 0.151 AC: 6281 AN: 41506

American (AMR) AF: 0.362 AC: 5531 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5174

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4816

European-Finnish (FIN) AF: 0.513 AC: 5412 AN: 10552

Middle Eastern (MID) AF: 0.428 AC: 124 AN: 290

European-Non Finnish (NFE) AF: 0.533 AC: 36219 AN: 67906

Other (OTH) AF: 0.405 AC: 852 AN: 2104

Alfa AF: 0.333 Hom.: 1037

Bravo AF: 0.368

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.30
PhyloP100		2.3
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: rs2661818; hg19: chr1-162264814;