rs743506

chr7-151009827-G-Achr7-151009827-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000603.5(NOS3):c.2512+242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,124 control chromosomes in the GnomAD database, including 39,020 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (39020 hom., cov: 32)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.2512+242G>A		intron_variant		ENST00000297494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.2512+242G>A		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000461406.5	c.1894+242G>A		intron_variant		2
NOS3	ENST00000475017.1	c.393+242G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107615 AN: 152006 Hom.: 38995 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.706

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.708 AC: 107688 AN: 152124 Hom.: 39020 Cov.: 32 AF XY: 0.714 AC XY: 53072 AN XY: 74368

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.708

Alfa AF: 0.738 Hom.: 40024

Bravo AF: 0.696

Asia WGS AF: 0.809 AC: 2810 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.0
Dann	Benign	0.28

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: rs743506; hg19: chr7-150706915; COSMIC: COSV52487605; COSMIC: COSV52487605;