7-151011214-G-T

Position:

• chr7-151011214-G-T

Variant summary

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

The NM_000603.5(NOS3):​c.2984+228G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 151,890 control chromosomes in the GnomAD database, including 44,959 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 0.77 (44959 hom., cov: 30)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.2984+228G>T		intron_variant		ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.2984+228G>T		intron_variant		1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116543 AN: 151772 Hom.: 44931 Cov.: 30

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.768 AC: 116626 AN: 151890 Hom.: 44959 Cov.: 30 AF XY: 0.772 AC XY: 57250 AN XY: 74202

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.755

Alfa AF: 0.751 Hom.: 52681

Bravo AF: 0.765

Asia WGS AF: 0.824 AC: 2867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.7
DANN	Benign	0.42

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: rs1808593; hg19: chr7-150708302;