rs10753765

Variant names:

• chr1-162181983-A-G
• rs10753765
• NM_014697.3:c.177+27507A>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.177+27507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,032 control chromosomes in the GnomAD database, including 24,728 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 0.54 (24728 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+27507A>G		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.177+27507A>G		intron_variant	Intron 2 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.177+27507A>G		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+27507A>G		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+27507A>G		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81993 AN: 151914 Hom.: 24699 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.540 AC: 82078 AN: 152032 Hom.: 24728 Cov.: 32 AF XY: 0.541 AC XY: 40180 AN XY: 74322

African (AFR) AF: 0.802 AC: 33268 AN: 41478

American (AMR) AF: 0.502 AC: 7668 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1990 AN: 3472

East Asian (EAS) AF: 0.772 AC: 3989 AN: 5166

South Asian (SAS) AF: 0.622 AC: 2996 AN: 4814

European-Finnish (FIN) AF: 0.372 AC: 3924 AN: 10552

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26648 AN: 67942

Other (OTH) AF: 0.522 AC: 1102 AN: 2112

Alfa AF: 0.474 Hom.: 2538

Bravo AF: 0.558

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.41
PhyloP100		-0.52
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: rs10753765; hg19: chr1-162151773;