1-162244077-T-C

Variant names:

• chr1-162244077-T-C
• rs10918963
• NM_014697.3:c.178-43267T>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.178-43267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,164 control chromosomes in the GnomAD database, including 4,165 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 0.22 (4165 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-43267T>C		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-43267T>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.178-43267T>C		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-43267T>C		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-43267T>C		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33481 AN: 152046 Hom.: 4167 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.220 AC: 33487 AN: 152164 Hom.: 4165 Cov.: 32 AF XY: 0.230 AC XY: 17140 AN XY: 74390

African (AFR) AF: 0.142 AC: 5875 AN: 41510

American (AMR) AF: 0.278 AC: 4250 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2660 AN: 5166

South Asian (SAS) AF: 0.350 AC: 1684 AN: 4814

European-Finnish (FIN) AF: 0.295 AC: 3131 AN: 10600

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14355 AN: 67992

Other (OTH) AF: 0.224 AC: 473 AN: 2116

Alfa AF: 0.213 Hom.: 4979

Bravo AF: 0.214

Asia WGS AF: 0.390 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		-0.026
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: rs10918963; hg19: chr1-162213867;