rs1800780

Variant names:

• chr7-151001791-A-G
• rs1800780
• NM_000603.5:c.1503-30A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000603.5(NOS3):​c.1503-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,372 control chromosomes in the GnomAD database, including 244,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (23841 hom., cov: 33)
  • Exomes 𝑓: 0.55 (220667 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.608
• Publications: 31 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-151001791-A-G is Benign according to our data. Variant chr7-151001791-A-G is described in ClinVar as Benign. ClinVar VariationId is 1262311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 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.1503-30A>G		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.1503-30A>G		intron	N/A	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.1503-30A>G		intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1503-30A>G		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.1503-30A>G		intron	N/A	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.1503-30A>G		intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84747 AN: 151980 Hom.: 23807 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.550

GnomAD2 exomes AF: 0.575 AC: 143498 AN: 249512 AF XY: 0.567

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.591

Gnomad EAS exome AF: 0.612

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.548 AC: 800580 AN: 1460274 Hom.: 220667 Cov.: 44 AF XY: 0.548 AC XY: 397936 AN XY: 726382

African (AFR) AF: 0.576 AC: 19252 AN: 33448

American (AMR) AF: 0.687 AC: 30679 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 15535 AN: 26118

East Asian (EAS) AF: 0.621 AC: 24653 AN: 39694

South Asian (SAS) AF: 0.564 AC: 48602 AN: 86222

European-Finnish (FIN) AF: 0.543 AC: 28570 AN: 52654

Middle Eastern (MID) AF: 0.500 AC: 2872 AN: 5748

European-Non Finnish (NFE) AF: 0.537 AC: 597329 AN: 1111358

Other (OTH) AF: 0.548 AC: 33088 AN: 60346

GnomAD4 genome AF: 0.558 AC: 84825 AN: 152098 Hom.: 23841 Cov.: 33 AF XY: 0.556 AC XY: 41377 AN XY: 74378

African (AFR) AF: 0.574 AC: 23834 AN: 41496

American (AMR) AF: 0.602 AC: 9209 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3472

East Asian (EAS) AF: 0.617 AC: 3186 AN: 5160

South Asian (SAS) AF: 0.562 AC: 2713 AN: 4826

European-Finnish (FIN) AF: 0.527 AC: 5589 AN: 10606

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36349 AN: 67932

Other (OTH) AF: 0.546 AC: 1153 AN: 2112

Alfa AF: 0.554 Hom.: 5659

Bravo AF: 0.568

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.61
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: rs1800780; hg19: chr7-150698879; COSMIC: COSV52487139; COSMIC: COSV52487139;