Variant 7-151002162-G-T 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.1648-38G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 1,468,152 control chromosomes in the GnomAD database, including 5,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 977 hom., cov: 31)

Exomes 𝑓: 0.080 ( 4804 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

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:

NOS3 (HGNC:):

NOS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 7-151002162-G-T is Benign according to our data. Variant chr7-151002162-G-T is described in ClinVar as [Benign]. Clinvar id is 1227505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NOS3	NM_000603.5 linkuse as main transcript	c.1648-38G>T	intron_variant	ENST00000297494.8	NP_000594.2	P29474-1
NOS3	NM_001160111.1 linkuse as main transcript	c.1648-38G>T	intron_variant		NP_001153583.1	P29474-2
NOS3	NM_001160110.1 linkuse as main transcript	c.1648-38G>T	intron_variant		NP_001153582.1	P29474-3
NOS3	NM_001160109.2 linkuse as main transcript	c.1648-38G>T	intron_variant		NP_001153581.1	P29474A0S0A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.1648-38G>T		intron_variant		1	NM_000603.5	ENSP00000297494.3		P29474-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16059

AN:

151930

Hom.:

979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0774

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0888

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0997

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0793

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.0927

AC:

16634

AN:

179452

Hom.:

868

AF XY:

0.0955

AC XY:

9139

AN XY:

95722

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.0591

Gnomad ASJ exome

AF:

0.0993

Gnomad EAS exome

AF:

0.0888

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0956

Gnomad NFE exome

AF:

0.0763

Gnomad OTH exome

AF:

0.0820

GnomAD4 exome

AF:

0.0803

AC:

105632

AN:

1316104

Hom.:

4804

Cov.:

AF XY:

0.0826

AC XY:

54069

AN XY:

654494

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0608

Gnomad4 ASJ exome

AF:

0.0980

Gnomad4 EAS exome

AF:

0.0948

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0919

Gnomad4 NFE exome

AF:

0.0719

Gnomad4 OTH exome

AF:

0.0851

GnomAD4 genome

AF:

0.106

AC:

16058

AN:

152048

Hom.:

977

Cov.:

AF XY:

0.107

AC XY:

7969

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.0772

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0888

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0997

Gnomad4 NFE

AF:

0.0793

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.0611

Hom.:

Bravo

AF:

0.105

Asia WGS

AF:

0.124

AC:

429

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

-0.92

CADD

Benign

0.48

DANN

Benign

0.60

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