NM_000603.5:c.1753-273A>G

Variant names:

• chr7-151006154-A-G
• rs2853795
• NM_000603.5:c.1753-273A>G

Variant summary

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

The NM_000603.5(NOS3):​c.1753-273A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,180 control chromosomes in the GnomAD database, including 2,851 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 0.16 (2851 hom., cov: 33)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.1753-273A>G		intron	N/A	NP_000594.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1753-273A>G		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000943234.1		c.1753-273A>G		intron	N/A	ENSP00000613293.1
	NOS3	ENST00000908206.1		c.1753-273A>G		intron	N/A	ENSP00000578265.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25014 AN: 152062 Hom.: 2837 Cov.: 33

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.165 AC: 25043 AN: 152180 Hom.: 2851 Cov.: 33 AF XY: 0.171 AC XY: 12727 AN XY: 74408

African (AFR) AF: 0.0505 AC: 2096 AN: 41538

American (AMR) AF: 0.341 AC: 5210 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1460 AN: 5172

South Asian (SAS) AF: 0.212 AC: 1020 AN: 4822

European-Finnish (FIN) AF: 0.241 AC: 2550 AN: 10594

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11701 AN: 68000

Other (OTH) AF: 0.161 AC: 340 AN: 2114

Alfa AF: 0.171 Hom.: 4373

Bravo AF: 0.172

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.66
PhyloP100		-0.13
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: rs2853795; hg19: chr7-150703242;