rs3918184

Variant names:

• chr7-151005131-C-T
• rs3918184
• NM_000603.5:c.1753-1296C>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.1753-1296C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,866 control chromosomes in the GnomAD database, including 9,511 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 0.35 (9511 hom., cov: 31)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1753-1296C>T		intron_variant	Intron 14 of 26	ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1753-1296C>T		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000461406.5	c.1135-1296C>T		intron_variant	Intron 11 of 23	2		ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52830 AN: 151748 Hom.: 9506 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.348 AC: 52847 AN: 151866 Hom.: 9511 Cov.: 31 AF XY: 0.341 AC XY: 25277 AN XY: 74198

African (AFR) AF: 0.381 AC: 15774 AN: 41416

American (AMR) AF: 0.241 AC: 3680 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1708 AN: 5138

South Asian (SAS) AF: 0.345 AC: 1651 AN: 4792

European-Finnish (FIN) AF: 0.275 AC: 2896 AN: 10534

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.358 AC: 24298 AN: 67952

Other (OTH) AF: 0.349 AC: 735 AN: 2104

Alfa AF: 0.357 Hom.: 32444

Bravo AF: 0.346

Asia WGS AF: 0.314 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.71
PhyloP100		-1.0
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: rs3918184; hg19: chr7-150702219;