rs4656349

Variant names:

• chr1-162080034-G-A
• rs4656349
• NM_014697.3:c.105+9752G>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.105+9752G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,994 control chromosomes in the GnomAD database, including 24,653 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 (24653 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.105+9752G>A		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.105+9752G>A		intron_variant	Intron 1 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.105+9752G>A		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.105+9752G>A		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.105+9752G>A		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82627 AN: 151876 Hom.: 24631 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.544 AC: 82681 AN: 151994 Hom.: 24653 Cov.: 32 AF XY: 0.543 AC XY: 40316 AN XY: 74290

African (AFR) AF: 0.303 AC: 12538 AN: 41428

American (AMR) AF: 0.587 AC: 8974 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2097 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2448 AN: 5166

South Asian (SAS) AF: 0.373 AC: 1794 AN: 4812

European-Finnish (FIN) AF: 0.658 AC: 6955 AN: 10564

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45957 AN: 67956

Other (OTH) AF: 0.553 AC: 1170 AN: 2114

Alfa AF: 0.579 Hom.: 21867

Bravo AF: 0.536

Asia WGS AF: 0.401 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.8
DANN	Benign	0.71
PhyloP100		0.25
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: rs4656349; hg19: chr1-162049824;