chr1-162287243-C-G

Variant names:

• chr1-162287243-C-G
• rs10800405
• NM_014697.3:c.178-101C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014697.3(NOS1AP):​c.178-101C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 808,154 control chromosomes in the GnomAD database, including 35,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6745 hom., cov: 32)
  • Exomes 𝑓: 0.28 (28272 hom.)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0950
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-162287243-C-G is Benign according to our data. Variant chr1-162287243-C-G is described in ClinVar as [Benign]. Clinvar id is 1248946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.178-101C>G		intron_variant	Intron 2 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.178-101C>G		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.178-101C>G		intron_variant	Intron 2 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.178-101C>G		intron_variant	Intron 2 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.178-101C>G		intron_variant	Intron 2 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43726 AN: 151884 Hom.: 6722 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.280 AC: 183644 AN: 656152 Hom.: 28272 AF XY: 0.282 AC XY: 99027 AN XY: 350678

African (AFR) AF: 0.305 AC: 5382 AN: 17620

American (AMR) AF: 0.367 AC: 14430 AN: 39356

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 5635 AN: 19588

East Asian (EAS) AF: 0.549 AC: 19434 AN: 35368

South Asian (SAS) AF: 0.366 AC: 23906 AN: 65364

European-Finnish (FIN) AF: 0.264 AC: 12710 AN: 48230

Middle Eastern (MID) AF: 0.297 AC: 1222 AN: 4110

European-Non Finnish (NFE) AF: 0.232 AC: 91319 AN: 393194

Other (OTH) AF: 0.288 AC: 9606 AN: 33322

GnomAD4 genome AF: 0.288 AC: 43802 AN: 152002 Hom.: 6745 Cov.: 32 AF XY: 0.295 AC XY: 21927 AN XY: 74296

African (AFR) AF: 0.301 AC: 12479 AN: 41406

American (AMR) AF: 0.355 AC: 5426 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3065 AN: 5166

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4812

European-Finnish (FIN) AF: 0.271 AC: 2859 AN: 10566

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.237 AC: 16112 AN: 67992

Other (OTH) AF: 0.291 AC: 615 AN: 2110

Alfa AF: 0.260 Hom.: 657

Bravo AF: 0.295

Asia WGS AF: 0.460 AC: 1601 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		0.095
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: rs10800405; hg19: chr1-162257033;