Variant 7-151007162-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000603.5(NOS3):c.1998C>G(p.Ala666Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,552 control chromosomes in the GnomAD database, including 72,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10911 hom., cov: 33)

Exomes 𝑓: 0.28 ( 61217 hom. )

Consequence

NOS3
NM_000603.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

NOS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 7-151007162-C-G is Benign according to our data. Variant chr7-151007162-C-G is described in ClinVar as [Benign]. Clinvar id is 403249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5 linkuse as main transcript	c.1998C>G	p.Ala666Ala	synonymous_variant	17/27	ENST00000297494.8	NP_000594.2	P29474-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.1998C>G	p.Ala666Ala	synonymous_variant	17/27	1	NM_000603.5	ENSP00000297494.3		P29474-1
NOS3	ENST00000461406.5 linkuse as main transcript	c.1380C>G	p.Ala460Ala	synonymous_variant	14/24	2		ENSP00000417143.1		E7ESA7

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54276

AN:

151992

Hom.:

10867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.345

AC:

86546

AN:

250728

Hom.:

17018

AF XY:

0.330

AC XY:

44801

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.511

Gnomad AMR exome

AF:

0.587

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.359

Gnomad SAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.276

AC:

403907

AN:

1461442

Hom.:

61217

Cov.:

AF XY:

0.277

AC XY:

201252

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.510

Gnomad4 AMR exome

AF:

0.575

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.357

AC:

54376

AN:

152110

Hom.:

10911

Cov.:

AF XY:

0.363

AC XY:

26992

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.503

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.233

Hom.:

1346

Bravo

AF:

0.376

Asia WGS

AF:

0.378

AC:

1312

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.244

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

NOS3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.1

DANN

Benign

0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over