rs3793342

Variant names:

• chr7-150998107-G-A
• rs3793342
• NM_000603.5:c.583-250G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000603.5(NOS3):​c.583-250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,220 control chromosomes in the GnomAD database, including 1,449 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 0.13 (1449 hom., cov: 32)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 19 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 (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.583-250G>A		intron_variant	Intron 5 of 26	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.583-250G>A		intron_variant	Intron 4 of 13		NP_001153583.1
NOS3	NM_001160110.1	c.583-250G>A		intron_variant	Intron 4 of 13		NP_001153582.1
NOS3	NM_001160109.2	c.583-250G>A		intron_variant	Intron 4 of 13		NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.583-250G>A		intron_variant	Intron 5 of 26	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000484524.5	c.583-250G>A		intron_variant	Intron 4 of 13	1		ENSP00000420215.1
NOS3	ENST00000467517.1	c.583-250G>A		intron_variant	Intron 4 of 13	1		ENSP00000420551.1
NOS3	ENST00000461406.5	c.-36-250G>A		intron_variant	Intron 2 of 23	2		ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19856 AN: 152102 Hom.: 1449 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.130 AC: 19859 AN: 152220 Hom.: 1449 Cov.: 32 AF XY: 0.131 AC XY: 9762 AN XY: 74434

African (AFR) AF: 0.0933 AC: 3877 AN: 41552

American (AMR) AF: 0.0998 AC: 1527 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3470

East Asian (EAS) AF: 0.108 AC: 560 AN: 5166

South Asian (SAS) AF: 0.146 AC: 707 AN: 4830

European-Finnish (FIN) AF: 0.180 AC: 1907 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10321 AN: 67998

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.140 Hom.: 620

Bravo AF: 0.122

Asia WGS AF: 0.123 AC: 426 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	0.040
DANN	Benign	0.66
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3793342; hg19: chr7-150695195;