Variant chr7-151013792-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000603.5(NOS3):c.3324G>C(p.Arg1108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,611,238 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 20 hom. )

Consequence

NOS3
NM_000603.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.555

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:

ATG9B (HGNC:21899): (autophagy related 9B) This gene functions in the regulation of autophagy, a lysosomal degradation pathway. This gene also functions as an antisense transcript in the posttranscriptional regulation of the endothelial nitric oxide synthase 3 gene, which has 3' overlap with this gene on the opposite strand. Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ATG9B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-151013792-G-C is Benign according to our data. Variant chr7-151013792-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 709432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.555 with no splicing effect.

BS2

High AC in GnomAd4 at 282 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NOS3	NM_000603.5 linkuse as main transcript	c.3324G>C	p.Arg1108=	synonymous_variant	26/27	ENST00000297494.8
ATG9B	NR_073169.1 linkuse as main transcript	n.2578C>G		non_coding_transcript_exon_variant	17/18
ATG9B	NR_133652.1 linkuse as main transcript	n.3315C>G		non_coding_transcript_exon_variant	16/17
ATG9B	XR_007060009.1 linkuse as main transcript	n.3358C>G		non_coding_transcript_exon_variant	14/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.3324G>C	p.Arg1108=	synonymous_variant	26/27	1	NM_000603.5	P1	P29474-1

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

282

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00198

AC:

479

AN:

242098

Hom.:

AF XY:

0.00215

AC XY:

283

AN XY:

131642

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.000882

Gnomad ASJ exome

AF:

0.00284

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00497

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.00170

AC:

2481

AN:

1458892

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

1298

AN XY:

725636

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00277

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00481

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00185

AC:

282

AN:

152346

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00187

Hom.:

Bravo

AF:

0.00147

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	NOS3: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.2

DANN

Benign

0.82

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