ENST00000493151.1:c.-88C>T

Variant names:

• chr1-162365262-C-T
• rs905721
• ENST00000493151.1:c.-88C>T

Variant summary

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

The ENST00000493151.1(NOS1AP):​c.-88C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,507,558 control chromosomes in the GnomAD database, including 100,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8491 hom., cov: 33)
  • Exomes 𝑓: 0.36 (92358 hom.)
• Consequence: NOS1AP ENST00000493151.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0430
• 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)

ENSG00000254706 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-162365262-C-T is Benign according to our data. Variant chr1-162365262-C-T is described in ClinVar as Benign. ClinVar VariationId is 1238681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 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.940-142C>T		intron	N/A	NP_055512.1
	NOS1AP	NM_001126060.2		c.-88C>T		5_prime_UTR	Exon 1 of 2	NP_001119532.2
	NOS1AP	NM_001164757.2		c.925-142C>T		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.-88C>T		5_prime_UTR	Exon 1 of 2	ENSP00000434988.1
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.940-142C>T		intron	N/A	ENSP00000355133.5
	NOS1AP	ENST00000530878.5	TSL:1	c.925-142C>T		intron	N/A	ENSP00000431586.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47134 AN: 152010 Hom.: 8483 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.364 AC: 493390 AN: 1355430 Hom.: 92358 Cov.: 58 AF XY: 0.361 AC XY: 239382 AN XY: 662908

African (AFR) AF: 0.112 AC: 3527 AN: 31470

American (AMR) AF: 0.435 AC: 14976 AN: 34390

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 6399 AN: 22014

East Asian (EAS) AF: 0.506 AC: 18389 AN: 36368

South Asian (SAS) AF: 0.245 AC: 17523 AN: 71506

European-Finnish (FIN) AF: 0.434 AC: 16801 AN: 38688

Middle Eastern (MID) AF: 0.278 AC: 1509 AN: 5428

European-Non Finnish (NFE) AF: 0.373 AC: 394774 AN: 1059042

Other (OTH) AF: 0.345 AC: 19492 AN: 56524

GnomAD4 genome AF: 0.310 AC: 47141 AN: 152128 Hom.: 8491 Cov.: 33 AF XY: 0.315 AC XY: 23408 AN XY: 74350

African (AFR) AF: 0.125 AC: 5205 AN: 41546

American (AMR) AF: 0.397 AC: 6071 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2680 AN: 5138

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4818

European-Finnish (FIN) AF: 0.445 AC: 4708 AN: 10572

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25251 AN: 67982

Other (OTH) AF: 0.319 AC: 673 AN: 2110

Alfa AF: 0.333 Hom.: 1211

Bravo AF: 0.303

Asia WGS AF: 0.347 AC: 1206 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 06, 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	-0.82
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		-0.043
PromoterAI		0.013	Neutral
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: rs905721; hg19: chr1-162335052; COSMIC: COSV62641562; COSMIC: COSV62641562;