Variant 7-151014025-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_000603.5(NOS3):c.3468C>T(p.His1156His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,613,066 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

NOS3
NM_000603.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.641

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:

ATG9B (HGNC:):

ATG9B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 7-151014025-C-T is Benign according to our data. Variant chr7-151014025-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 741463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-151014025-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.641 with no splicing effect.

BS2

High AC in GnomAd4 at 108 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5 linkuse as main transcript	c.3468C>T	p.His1156His	synonymous_variant	27/27	ENST00000297494.8	NP_000594.2	P29474-1
ATG9B	XR_007060009.1 linkuse as main transcript	n.3125G>A		non_coding_transcript_exon_variant	14/15
ATG9B	NR_073169.1 linkuse as main transcript	n.2457+57G>A		intron_variant
ATG9B	NR_133652.1 linkuse as main transcript	n.3194+57G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.3468C>T	p.His1156His	synonymous_variant	27/27	1	NM_000603.5	ENSP00000297494.3		P29474-1
ATG9B	ENST00000605952.5 linkuse as main transcript	n.*343+57G>A		intron_variant		1		ENSP00000475737.2		Q674R7-1

Frequencies

GnomAD3 genomes

AF:

0.000709

AC:

108

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000571

AC:

143

AN:

250646

Hom.:

AF XY:

0.000634

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00133

AC:

1945

AN:

1460726

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

983

AN XY:

726492

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.000912

GnomAD4 genome

AF:

0.000709

AC:

108

AN:

152340

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000676

EpiCase

AF:

0.00125

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 09, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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