1-162343728-A-G

Variant names:

• chr1-162343728-A-G
• rs3751285
• NM_014697.3:c.454-107A>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.454-107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,317,090 control chromosomes in the GnomAD database, including 58,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6999 hom., cov: 34)
  • Exomes 𝑓: 0.29 (51121 hom.)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.384
• Publications: 7 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=-0.86).
• BP6: Variant 1-162343728-A-G is Benign according to our data. Variant chr1-162343728-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.454-107A>G		intron	N/A	NP_055512.1
	NOS1AP	NM_001164757.2		c.439-107A>G		intron	N/A	NP_001158229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.454-107A>G		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.439-107A>G		intron	N/A	ENSP00000431586.1
	NOS1AP	ENST00000430120.3	TSL:1	n.439-107A>G		intron	N/A	ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45154 AN: 152014 Hom.: 6986 Cov.: 34

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.289 AC: 337243 AN: 1164956 Hom.: 51121 AF XY: 0.290 AC XY: 172303 AN XY: 594102

African (AFR) AF: 0.265 AC: 7375 AN: 27868

American (AMR) AF: 0.436 AC: 19205 AN: 44040

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7168 AN: 24254

East Asian (EAS) AF: 0.503 AC: 19166 AN: 38090

South Asian (SAS) AF: 0.318 AC: 25207 AN: 79364

European-Finnish (FIN) AF: 0.325 AC: 17173 AN: 52862

Middle Eastern (MID) AF: 0.252 AC: 1306 AN: 5192

European-Non Finnish (NFE) AF: 0.268 AC: 225780 AN: 842674

Other (OTH) AF: 0.294 AC: 14863 AN: 50612

GnomAD4 genome AF: 0.297 AC: 45208 AN: 152134 Hom.: 6999 Cov.: 34 AF XY: 0.305 AC XY: 22661 AN XY: 74368

African (AFR) AF: 0.272 AC: 11266 AN: 41494

American (AMR) AF: 0.380 AC: 5808 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2763 AN: 5178

South Asian (SAS) AF: 0.316 AC: 1527 AN: 4830

European-Finnish (FIN) AF: 0.327 AC: 3452 AN: 10564

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18410 AN: 67986

Other (OTH) AF: 0.303 AC: 641 AN: 2116

Alfa AF: 0.294 Hom.: 2883

Bravo AF: 0.299

Asia WGS AF: 0.372 AC: 1291 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.38
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: rs3751285; hg19: chr1-162313518; COSMIC: COSV62638128; COSMIC: COSV62638128;