Variant rs1007311 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000603.5(NOS3):c.817-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,595,936 control chromosomes in the GnomAD database, including 158,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.46 ( 16531 hom., cov: 31)

Exomes 𝑓: 0.44 ( 141703 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.51

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-150998920-A-G is Benign according to our data. Variant chr7-150998920-A-G is described in ClinVar as [Benign]. Clinvar id is 1256933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NOS3	NM_000603.5 linkuse as main transcript	c.817-26A>G	intron_variant	ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2 linkuse as main transcript	c.817-26A>G	intron_variant		NP_001153581.1
NOS3	NM_001160110.1 linkuse as main transcript	c.817-26A>G	intron_variant		NP_001153582.1
NOS3	NM_001160111.1 linkuse as main transcript	c.817-26A>G	intron_variant		NP_001153583.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.817-26A>G	intron_variant	1	NM_000603.5	ENSP00000297494	P1	P29474-1
NOS3	ENST00000467517.1 linkuse as main transcript	c.817-26A>G	intron_variant	1		ENSP00000420551		P29474-3
NOS3	ENST00000484524.5 linkuse as main transcript	c.817-26A>G	intron_variant	1		ENSP00000420215		P29474-2
NOS3	ENST00000461406.5 linkuse as main transcript	c.199-26A>G	intron_variant	2		ENSP00000417143

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69590

AN:

151714

Hom.:

16515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.456

GnomAD3 exomes

AF:

0.431

AC:

101194

AN:

234618

Hom.:

22958

AF XY:

0.438

AC XY:

56163

AN XY:

128348

show subpopulations

Gnomad AFR exome

AF:

0.564

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.521

Gnomad SAS exome

AF:

0.493

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.440

AC:

634701

AN:

1444106

Hom.:

141703

Cov.:

AF XY:

0.442

AC XY:

317001

AN XY:

717558

show subpopulations

Gnomad4 AFR exome

AF:

0.564

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.564

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.494

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.435

Gnomad4 OTH exome

AF:

0.457

GnomAD4 genome

AF:

0.459

AC:

69631

AN:

151830

Hom.:

16531

Cov.:

AF XY:

0.454

AC XY:

33670

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.559

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.432

Gnomad4 OTH

AF:

0.460

Alfa

AF:

0.462

Hom.:

3095

Bravo

AF:

0.458

Asia WGS

AF:

0.493

AC:

1714

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.047

DANN

Benign

0.36

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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