1-162080087-T-G

Variant names:

• chr1-162080087-T-G
• rs11579080
• NM_014697.3:c.105+9805T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014697.3(NOS1AP):​c.105+9805T>G 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 152,120 control chromosomes in the GnomAD database, including 24,674 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 (24674 hom., cov: 33)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• 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+9805T>G		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.105+9805T>G		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+9805T>G		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.105+9805T>G		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.105+9805T>G		intron_variant	Intron 1 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82662 AN: 152002 Hom.: 24652 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.544 AC: 82717 AN: 152120 Hom.: 24674 Cov.: 33 AF XY: 0.543 AC XY: 40362 AN XY: 74378

African (AFR) AF: 0.301 AC: 12495 AN: 41508

American (AMR) AF: 0.591 AC: 9039 AN: 15288

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

East Asian (EAS) AF: 0.474 AC: 2455 AN: 5174

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4818

European-Finnish (FIN) AF: 0.658 AC: 6971 AN: 10598

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

European-Non Finnish (NFE) AF: 0.676 AC: 45948 AN: 67952

Other (OTH) AF: 0.553 AC: 1168 AN: 2112

Alfa AF: 0.509 Hom.: 6801

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	-0.24
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		0.66
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: rs11579080; hg19: chr1-162049877;