1-162216760-T-C

Variant names:

• chr1-162216760-T-C
• rs4531275
• NM_014697.3:c.177+62284T>C

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+62284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,094 control chromosomes in the GnomAD database, including 26,453 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 0.58 (26453 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.177+62284T>C		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.177+62284T>C		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+62284T>C		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.177+62284T>C		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.177+62284T>C		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88273 AN: 151976 Hom.: 26443 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.581 AC: 88319 AN: 152094 Hom.: 26453 Cov.: 33 AF XY: 0.573 AC XY: 42626 AN XY: 74330

African (AFR) AF: 0.443 AC: 18368 AN: 41496

American (AMR) AF: 0.571 AC: 8734 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 2001 AN: 3472

East Asian (EAS) AF: 0.487 AC: 2524 AN: 5186

South Asian (SAS) AF: 0.452 AC: 2178 AN: 4814

European-Finnish (FIN) AF: 0.612 AC: 6455 AN: 10542

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46016 AN: 67972

Other (OTH) AF: 0.602 AC: 1273 AN: 2116

Alfa AF: 0.642 Hom.: 41571

Bravo AF: 0.576

Asia WGS AF: 0.472 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.18
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: rs4531275; hg19: chr1-162186550;