rs1799983

Variant names:

• chr7-150999023-T-G
• rs1799983
• NM_000603.5:c.894T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-150999023-T-G
• chr7-150999023-T-A

Variant summary

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

The NM_001160110.1(NOS3):​c.894T>G​(p.Asp298Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 1,612,084 control chromosomes in the GnomAD database, including 399,768 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44214 hom., cov: 30)
  • Exomes 𝑓: 0.69 (355554 hom.)
• Consequence: NOS3 NM_001160110.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.502
• Publications: 1918 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 (MetaRNN=8.4196944E-7).
• BP6: Variant 7-150999023-T-G is Benign according to our data. Variant chr7-150999023-T-G is described in ClinVar as Benign. ClinVar VariationId is 14015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160110.1. 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.894T>G	p.Asp298Glu	missense	Exon 8 of 27	NP_000594.2
	NOS3	NM_001160111.1		c.894T>G	p.Asp298Glu	missense	Exon 7 of 14	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.894T>G	p.Asp298Glu	missense	Exon 7 of 14	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.894T>G	p.Asp298Glu	missense	Exon 8 of 27	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.894T>G	p.Asp298Glu	missense	Exon 7 of 14	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.894T>G	p.Asp298Glu	missense	Exon 7 of 14	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114696 AN: 151842 Hom.: 44151 Cov.: 30

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.745

GnomAD2 exomes AF: 0.751 AC: 187223 AN: 249394 AF XY: 0.745

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.791

Gnomad EAS exome AF: 0.892

Gnomad FIN exome AF: 0.707

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.694 AC: 1013298 AN: 1460126 Hom.: 355554 Cov.: 63 AF XY: 0.697 AC XY: 506539 AN XY: 726378

African (AFR) AF: 0.892 AC: 29851 AN: 33464

American (AMR) AF: 0.809 AC: 36132 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 20672 AN: 26120

East Asian (EAS) AF: 0.906 AC: 35962 AN: 39698

South Asian (SAS) AF: 0.815 AC: 70283 AN: 86234

European-Finnish (FIN) AF: 0.714 AC: 37192 AN: 52072

Middle Eastern (MID) AF: 0.746 AC: 4301 AN: 5766

European-Non Finnish (NFE) AF: 0.662 AC: 735651 AN: 1111776

Other (OTH) AF: 0.717 AC: 43254 AN: 60358

GnomAD4 genome AF: 0.756 AC: 114817 AN: 151958 Hom.: 44214 Cov.: 30 AF XY: 0.758 AC XY: 56247 AN XY: 74240

African (AFR) AF: 0.886 AC: 36756 AN: 41472

American (AMR) AF: 0.744 AC: 11366 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2794 AN: 3464

East Asian (EAS) AF: 0.888 AC: 4556 AN: 5132

South Asian (SAS) AF: 0.821 AC: 3953 AN: 4816

European-Finnish (FIN) AF: 0.706 AC: 7453 AN: 10562

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45448 AN: 67922

Other (OTH) AF: 0.747 AC: 1576 AN: 2110

Alfa AF: 0.715 Hom.: 21119

Bravo AF: 0.765

TwinsUK AF: 0.657 AC: 2438

ALSPAC AF: 0.648 AC: 2498

ESP6500AA AF: 0.884 AC: 3897

ESP6500EA AF: 0.676 AC: 5803

ExAC AF: 0.751 AC: 90786

Asia WGS AF: 0.850 AC: 2954 AN: 3478

EpiCase AF: 0.663

EpiControl AF: 0.662

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Ischemic stroke;C1863052:Alzheimer disease type 1;C5574918:Preeclampsia/eclampsia 1;CN305331:Essential hypertension, genetic (2)
-	-	2	not provided (2)
-	-	1	CORONARY ARTERY SPASM 1, SUSCEPTIBILITY TO (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.22
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	8.4e-7	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.50
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.057
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.048
MutPred		0.43		Loss of sheet (P = 0.0817)
MPC		0.061
ClinPred		0.00013	T
GERP RS		1.0
Varity_R		0.013
gMVP		0.53
Mutation Taster		=98/2	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: rs1799983; hg19: chr7-150696111; COSMIC: COSV52494140; COSMIC: COSV52494140;