rs76204833

Variant names:

• chr1-162128539-A-C
• rs76204833
• NM_014697.3:c.106-25866A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-162128539-A-C
• chr1-162128539-A-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.106-25866A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 152,230 control chromosomes in the GnomAD database, including 283 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 0.057 (283 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 1 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)

LOC105371475 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.106-25866A>C		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.106-25866A>C		intron	N/A	NP_001158229.1	O75052-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.106-25866A>C		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.106-25866A>C		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.106-25866A>C		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8598 AN: 152112 Hom.: 283 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0573

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

GnomAD4 genome AF: 0.0565 AC: 8602 AN: 152230 Hom.: 283 Cov.: 32 AF XY: 0.0554 AC XY: 4128 AN XY: 74458

African (AFR) AF: 0.0544 AC: 2261 AN: 41538

American (AMR) AF: 0.0462 AC: 707 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0476 AC: 230 AN: 4830

European-Finnish (FIN) AF: 0.0584 AC: 619 AN: 10592

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0648 AC: 4409 AN: 67994

Other (OTH) AF: 0.0567 AC: 120 AN: 2116

Alfa AF: 0.0611 Hom.: 155

Bravo AF: 0.0539

Asia WGS AF: 0.0230 AC: 78 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		-0.23
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: rs76204833; hg19: chr1-162098329;