1-162154155-G-C

Variant names:

• chr1-162154155-G-C
• rs10918776
• NM_014697.3:c.106-250G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014697.3(NOS1AP):​c.106-250G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,938 control chromosomes in the GnomAD database, including 5,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5741 hom., cov: 31)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79
• 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)

ENSG00000285636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-162154155-G-C is Benign according to our data. Variant chr1-162154155-G-C is described in ClinVar as [Benign]. Clinvar id is 1222171.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.106-250G>C		intron_variant	Intron 1 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.106-250G>C		intron_variant	Intron 1 of 9		NP_001158229.1
LOC105371475	XR_007066697.1	n.486+14127C>G		intron_variant	Intron 3 of 3
LOC105371475	XR_007066699.1	n.486+14127C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.106-250G>C		intron_variant	Intron 1 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.106-250G>C		intron_variant	Intron 1 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.106-250G>C		intron_variant	Intron 1 of 10	1		ENSP00000396713.3
ENSG00000285636	ENST00000648032.1	n.439-6437C>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39614 AN: 151820 Hom.: 5736 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.261 AC: 39627 AN: 151938 Hom.: 5741 Cov.: 31 AF XY: 0.269 AC XY: 19987 AN XY: 74242

African (AFR) AF: 0.280 AC: 11596 AN: 41430

American (AMR) AF: 0.271 AC: 4143 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2928 AN: 5156

South Asian (SAS) AF: 0.490 AC: 2355 AN: 4810

European-Finnish (FIN) AF: 0.288 AC: 3027 AN: 10528

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13987 AN: 67950

Other (OTH) AF: 0.248 AC: 523 AN: 2112

Alfa AF: 0.102 Hom.: 143

Bravo AF: 0.254

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.094
DANN	Benign	0.73
PhyloP100		-1.8
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: rs10918776; hg19: chr1-162123945;