Variant chr7-151010400-C-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.2685+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,117,416 control chromosomes in the GnomAD database, including 327,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 44995 hom., cov: 34)

Exomes 𝑓: 0.76 ( 282709 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.810

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:

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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=-0.76).

BP6

Variant 7-151010400-C-T is Benign according to our data. Variant chr7-151010400-C-T is described in ClinVar as [Benign]. Clinvar id is 1248545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.812 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.2685+113C>T		intron_variant		ENST00000297494.8	NP_000594.2	P29474-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.2685+113C>T	intron_variant	1	NM_000603.5	ENSP00000297494.3	P29474-1
NOS3	ENST00000461406.5 linkuse as main transcript	c.2067+113C>T	intron_variant	2		ENSP00000417143.1	E7ESA7
NOS3	ENST00000475017.1 linkuse as main transcript	c.564+113C>T	intron_variant	2		ENSP00000418245.1	H7C4V4

Frequencies

GnomAD3 genomes

AF:

0.767

AC:

116704

AN:

152104

Hom.:

44967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.842

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.732

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.834

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.754

Gnomad OTH

AF:

0.755

GnomAD4 exome

AF:

0.764

AC:

737495

AN:

965194

Hom.:

282709

Cov.:

AF XY:

0.766

AC XY:

370179

AN XY:

483214

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.828

Gnomad4 ASJ exome

AF:

0.716

Gnomad4 EAS exome

AF:

0.816

Gnomad4 SAS exome

AF:

0.842

Gnomad4 FIN exome

AF:

0.834

Gnomad4 NFE exome

AF:

0.750

Gnomad4 OTH exome

AF:

0.765

GnomAD4 genome

AF:

0.767

AC:

116788

AN:

152222

Hom.:

44995

Cov.:

AF XY:

0.771

AC XY:

57378

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.758

Gnomad4 AMR

AF:

0.780

Gnomad4 ASJ

AF:

0.732

Gnomad4 EAS

AF:

0.787

Gnomad4 SAS

AF:

0.834

Gnomad4 FIN

AF:

0.834

Gnomad4 NFE

AF:

0.754

Gnomad4 OTH

AF:

0.757

Alfa

AF:

0.753

Hom.:

58865

Bravo

AF:

0.764

Asia WGS

AF:

0.824

AC:

2865

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

-0.76

CADD

Benign

1.9

DANN

Benign

0.73

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