rs3918181

Variant names:

• chr7-151004695-G-A
• rs3918181
• NM_000603.5:c.1753-1732G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151004695-G-A
• chr7-151004695-G-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.1753-1732G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,032 control chromosomes in the GnomAD database, including 9,487 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 (9487 hom., cov: 33)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 13 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=-0.91).
• 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.1753-1732G>A		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.1753-1732G>A		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000461406.5	c.1135-1732G>A		intron_variant	Intron 11 of 23	2		ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52812 AN: 151914 Hom.: 9482 Cov.: 33

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.347 AC: 52829 AN: 152032 Hom.: 9487 Cov.: 33 AF XY: 0.340 AC XY: 25272 AN XY: 74308

African (AFR) AF: 0.381 AC: 15790 AN: 41454

American (AMR) AF: 0.241 AC: 3682 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1607 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1726 AN: 5172

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4824

European-Finnish (FIN) AF: 0.275 AC: 2903 AN: 10550

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24298 AN: 67974

Other (OTH) AF: 0.350 AC: 737 AN: 2108

Alfa AF: 0.364 Hom.: 2525

Bravo AF: 0.346

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.69
PhyloP100		-1.1
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: rs3918181; hg19: chr7-150701783;