chr1-162314267-A-G

Variant names:

• chr1-162314267-A-G
• rs2819328
• NM_014697.3:c.344+13561A>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.344+13561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,268 control chromosomes in the GnomAD database, including 60,314 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 0.88 (60314 hom., cov: 34)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 5 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.344+13561A>G		intron_variant	Intron 4 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.329+13561A>G		intron_variant	Intron 4 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.344+13561A>G		intron_variant	Intron 4 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.329+13561A>G		intron_variant	Intron 4 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.329+13561A>G		intron_variant	Intron 4 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134127 AN: 152150 Hom.: 60301 Cov.: 34

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.881 AC: 134185 AN: 152268 Hom.: 60314 Cov.: 34 AF XY: 0.885 AC XY: 65858 AN XY: 74450

African (AFR) AF: 0.679 AC: 28173 AN: 41508

American (AMR) AF: 0.951 AC: 14552 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3306 AN: 3472

East Asian (EAS) AF: 0.930 AC: 4812 AN: 5172

South Asian (SAS) AF: 0.916 AC: 4421 AN: 4824

European-Finnish (FIN) AF: 0.984 AC: 10451 AN: 10626

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65495 AN: 68042

Other (OTH) AF: 0.912 AC: 1927 AN: 2114

Alfa AF: 0.937 Hom.: 113541

Bravo AF: 0.871

Asia WGS AF: 0.911 AC: 3170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.0
DANN	Benign	0.83
PhyloP100		-1.0
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: rs2819328; hg19: chr1-162284057;