rs891511

Positions:

• chr7-151007755-G-A
• chr7-151007755-G-C
• chr7-151007755-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.2112+479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,168 control chromosomes in the GnomAD database, including 15,460 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 0.44 (15460 hom., cov: 34)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

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 (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.2112+479G>A		intron_variant		ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.2112+479G>A		intron_variant		1	NM_000603.5	ENSP00000297494	P1
NOS3	ENST00000461406.5	c.1494+479G>A		intron_variant		2		ENSP00000417143

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66327 AN: 152050 Hom.: 15426 Cov.: 34

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.436 AC: 66408 AN: 152168 Hom.: 15460 Cov.: 34 AF XY: 0.443 AC XY: 32983 AN XY: 74376

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.405

Alfa AF: 0.345 Hom.: 10855

Bravo AF: 0.448

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.94
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs891511; hg19: chr7-150704843;