rs1963645

Variant names:

• chr1-162364200-A-G
• rs1963645
• ENST00000493151.1:c.-1150A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493151.1(NOS1AP):​c.-1150A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 985,208 control chromosomes in the GnomAD database, including 62,388 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 0.34 (8801 hom., cov: 32)
  • Exomes 𝑓: 0.36 (53587 hom.)
• Consequence: NOS1AP ENST00000493151.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000493151.1. 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.940-1204A>G		intron	N/A	NP_055512.1
	NOS1AP	NM_001126060.2		c.-1150A>G		5_prime_UTR	Exon 1 of 2	NP_001119532.2
	NOS1AP	NM_001164757.2		c.925-1204A>G		intron	N/A	NP_001158229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000493151.1	TSL:1	c.-1150A>G		5_prime_UTR	Exon 1 of 2	ENSP00000434988.1
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.940-1204A>G		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.925-1204A>G		intron	N/A	ENSP00000431586.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 50983 AN: 151958 Hom.: 8800 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.358 AC: 298063 AN: 833128 Hom.: 53587 Cov.: 29 AF XY: 0.358 AC XY: 137653 AN XY: 384724

African (AFR) AF: 0.321 AC: 5063 AN: 15786

American (AMR) AF: 0.280 AC: 276 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 2501 AN: 5154

East Asian (EAS) AF: 0.207 AC: 750 AN: 3630

South Asian (SAS) AF: 0.398 AC: 6543 AN: 16460

European-Finnish (FIN) AF: 0.331 AC: 98 AN: 296

Middle Eastern (MID) AF: 0.444 AC: 720 AN: 1620

European-Non Finnish (NFE) AF: 0.357 AC: 272302 AN: 761898

Other (OTH) AF: 0.359 AC: 9810 AN: 27300

GnomAD4 genome AF: 0.335 AC: 50998 AN: 152080 Hom.: 8801 Cov.: 32 AF XY: 0.330 AC XY: 24570 AN XY: 74368

African (AFR) AF: 0.310 AC: 12867 AN: 41486

American (AMR) AF: 0.308 AC: 4713 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1736 AN: 3472

East Asian (EAS) AF: 0.193 AC: 998 AN: 5164

South Asian (SAS) AF: 0.377 AC: 1815 AN: 4820

European-Finnish (FIN) AF: 0.282 AC: 2980 AN: 10586

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24557 AN: 67964

Other (OTH) AF: 0.381 AC: 803 AN: 2108

Alfa AF: 0.358 Hom.: 16315

Bravo AF: 0.334

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.79
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: rs1963645; hg19: chr1-162333990;