rs1800780

chr7-151001791-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000603.5(NOS3):c.1503-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,372 control chromosomes in the GnomAD database, including 244,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (23841 hom., cov: 33)
  • Exomes 𝑓: 0.55 (220667 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.608

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-151001791-A-G is Benign according to our data. Variant chr7-151001791-A-G is described in ClinVar as [Benign]. Clinvar id is 1262311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.1503-30A>G		intron_variant		ENST00000297494.8
NOS3	NM_001160109.2	c.1503-30A>G		intron_variant
NOS3	NM_001160110.1	c.1503-30A>G		intron_variant
NOS3	NM_001160111.1	c.1503-30A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.1503-30A>G		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000467517.1	c.1503-30A>G		intron_variant		1
NOS3	ENST00000484524.5	c.1503-30A>G		intron_variant		1
NOS3	ENST00000461406.5	c.885-30A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84747 AN: 151980 Hom.: 23807 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.575 AC: 143498 AN: 249512 Hom.: 41653 AF XY: 0.567 AC XY: 76499 AN XY: 135026

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.591

Gnomad EAS exome AF: 0.612

Gnomad SAS exome AF: 0.567

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.548 AC: 800580 AN: 1460274 Hom.: 220667 Cov.: 44 AF XY: 0.548 AC XY: 397936 AN XY: 726382

Gnomad4 AFR exome AF: 0.576

Gnomad4 AMR exome AF: 0.687

Gnomad4 ASJ exome AF: 0.595

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.558 AC: 84825 AN: 152098 Hom.: 23841 Cov.: 33 AF XY: 0.556 AC XY: 41377 AN XY: 74378

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.546

Alfa AF: 0.554 Hom.: 5659

Bravo AF: 0.568

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.50

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

Other links and lift over

dbSNP: rs1800780; hg19: chr7-150698879; COSMIC: COSV52487139; COSMIC: COSV52487139;