7-150992309-A-T

Position:

• chr7-150992309-A-T

Variant summary

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

The NM_000603.5(NOS3):​c.-52+1009A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,970 control chromosomes in the GnomAD database, including 29,973 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 0.62 (29973 hom., cov: 31)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.-52+1009A>T		intron_variant		ENST00000297494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.-52+1009A>T		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000461406.5	c.-149+1009A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94660 AN: 151850 Hom.: 29946 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.623 AC: 94731 AN: 151970 Hom.: 29973 Cov.: 31 AF XY: 0.629 AC XY: 46768 AN XY: 74298

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.601

Alfa AF: 0.513 Hom.: 1503

Bravo AF: 0.624

Asia WGS AF: 0.811 AC: 2821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.78

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: rs1800783; hg19: chr7-150689397;