1-162364310-T-C

Variant names:

• chr1-162364310-T-C
• rs905720
• ENST00000493151.1:c.-1040T>C

Variant summary

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

The NM_001126060.2(NOS1AP):​c.-1040T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 985,162 control chromosomes in the GnomAD database, including 249,549 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 0.65 (33046 hom., cov: 32)
  • Exomes 𝑓: 0.72 (216503 hom.)
• Consequence: NOS1AP NM_001126060.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126060.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.940-1094T>C		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001126060.2		c.-1040T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_001119532.2	O75052-2
	NOS1AP	NM_001126060.2		c.-1040T>C		5_prime_UTR	Exon 1 of 2	NP_001119532.2	O75052-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000493151.1	TSL:1	c.-1040T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000434988.1	O75052-2
	NOS1AP	ENST00000493151.1	TSL:1	c.-1040T>C		5_prime_UTR	Exon 1 of 2	ENSP00000434988.1	O75052-2
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.940-1094T>C		intron	N/A	ENSP00000355133.5	O75052-1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98301 AN: 151938 Hom.: 33041 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.719 AC: 599306 AN: 833106 Hom.: 216503 Cov.: 40 AF XY: 0.719 AC XY: 276559 AN XY: 384716

African (AFR) AF: 0.429 AC: 6779 AN: 15788

American (AMR) AF: 0.716 AC: 705 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 3981 AN: 5154

East Asian (EAS) AF: 0.709 AC: 2575 AN: 3630

South Asian (SAS) AF: 0.615 AC: 10131 AN: 16460

European-Finnish (FIN) AF: 0.738 AC: 211 AN: 286

Middle Eastern (MID) AF: 0.717 AC: 1161 AN: 1620

European-Non Finnish (NFE) AF: 0.728 AC: 554687 AN: 761890

Other (OTH) AF: 0.699 AC: 19076 AN: 27294

GnomAD4 genome AF: 0.647 AC: 98327 AN: 152056 Hom.: 33046 Cov.: 32 AF XY: 0.646 AC XY: 48045 AN XY: 74342

African (AFR) AF: 0.445 AC: 18430 AN: 41450

American (AMR) AF: 0.708 AC: 10816 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2703 AN: 3470

East Asian (EAS) AF: 0.713 AC: 3687 AN: 5170

South Asian (SAS) AF: 0.599 AC: 2887 AN: 4816

European-Finnish (FIN) AF: 0.728 AC: 7690 AN: 10570

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49713 AN: 67982

Other (OTH) AF: 0.697 AC: 1471 AN: 2110

Alfa AF: 0.701 Hom.: 47790

Bravo AF: 0.639

Asia WGS AF: 0.621 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.0
DANN	Benign	0.84
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: rs905720; hg19: chr1-162334100;