chr1-162332845-T-C

Variant names:

• chr1-162332845-T-C
• rs347306
• NM_014697.3:c.345-172T>C

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.345-172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,090 control chromosomes in the GnomAD database, including 16,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.45 (16490 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00500
• 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=-0.87).
• BP6: Variant 1-162332845-T-C is Benign according to our data. Variant chr1-162332845-T-C is described in ClinVar as [Benign]. Clinvar id is 1298248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS1AP	NM_014697.3	c.345-172T>C		intron_variant	Intron 4 of 9	ENST00000361897.10	NP_055512.1
NOS1AP	NM_001164757.2	c.330-172T>C		intron_variant	Intron 4 of 9		NP_001158229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS1AP	ENST00000361897.10	c.345-172T>C		intron_variant	Intron 4 of 9	1	NM_014697.3	ENSP00000355133.5
NOS1AP	ENST00000530878.5	c.330-172T>C		intron_variant	Intron 4 of 9	1		ENSP00000431586.1
NOS1AP	ENST00000430120.3	n.330-172T>C		intron_variant	Intron 4 of 10	1		ENSP00000396713.3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68565 AN: 151972 Hom.: 16488 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.482

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.451 AC: 68573 AN: 152090 Hom.: 16490 Cov.: 32 AF XY: 0.443 AC XY: 32934 AN XY: 74342

African (AFR) AF: 0.306 AC: 12685 AN: 41482

American (AMR) AF: 0.455 AC: 6954 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5172

South Asian (SAS) AF: 0.342 AC: 1652 AN: 4824

European-Finnish (FIN) AF: 0.463 AC: 4882 AN: 10554

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38111 AN: 67984

Other (OTH) AF: 0.480 AC: 1013 AN: 2110

Alfa AF: 0.518 Hom.: 26162

Bravo AF: 0.447

Asia WGS AF: 0.312 AC: 1087 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 04, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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	-0.87
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		0.0050
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: rs347306; hg19: chr1-162302635; COSMIC: COSV107450428;