7-150992309-A-T

Variant names:

• chr7-150992309-A-T
• rs1800783
• NM_000603.5:c.-52+1009A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.-52+1009A>T		intron	N/A	NP_000594.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.-52+1009A>T		intron	N/A	ENSP00000297494.3
	NOS3	ENST00000461406.5	TSL:2	c.-149+1009A>T		intron	N/A	ENSP00000417143.1

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

African (AFR) AF: 0.568 AC: 23543 AN: 41414

American (AMR) AF: 0.659 AC: 10060 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2177 AN: 3470

East Asian (EAS) AF: 0.890 AC: 4601 AN: 5172

South Asian (SAS) AF: 0.768 AC: 3702 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6875 AN: 10564

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41686 AN: 67948

Other (OTH) AF: 0.601 AC: 1268 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.78
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800783; hg19: chr7-150689397;