rs1549758

Variant names:

• chr7-150998638-T-C
• rs1549758
• NM_000603.5:c.774T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-150998638-T-C
• chr7-150998638-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000603.5(NOS3):​c.774T>C​(p.Asp258Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,607,270 control chromosomes in the GnomAD database, including 411,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44840 hom., cov: 33)
  • Exomes 𝑓: 0.71 (366949 hom.)
• Consequence: NOS3 NM_000603.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.51
• Publications: 67 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 7-150998638-T-C is Benign according to our data. Variant chr7-150998638-T-C is described in ClinVar as Benign. ClinVar VariationId is 403248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 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.774T>C	p.Asp258Asp	synonymous	Exon 7 of 27	NP_000594.2
	NOS3	NM_001160111.1		c.774T>C	p.Asp258Asp	synonymous	Exon 6 of 14	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.774T>C	p.Asp258Asp	synonymous	Exon 6 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.774T>C	p.Asp258Asp	synonymous	Exon 7 of 27	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.774T>C	p.Asp258Asp	synonymous	Exon 6 of 14	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.774T>C	p.Asp258Asp	synonymous	Exon 6 of 14	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115782 AN: 152070 Hom.: 44777 Cov.: 33

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.749

GnomAD2 exomes AF: 0.759 AC: 177937 AN: 234452 AF XY: 0.756

Gnomad AFR exome AF: 0.889

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.798

Gnomad EAS exome AF: 0.819

Gnomad FIN exome AF: 0.719

Gnomad NFE exome AF: 0.690

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.707 AC: 1028749 AN: 1455082 Hom.: 366949 Cov.: 72 AF XY: 0.711 AC XY: 514631 AN XY: 723366

African (AFR) AF: 0.889 AC: 29754 AN: 33460

American (AMR) AF: 0.814 AC: 35796 AN: 43956

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 20724 AN: 25962

East Asian (EAS) AF: 0.852 AC: 33661 AN: 39524

South Asian (SAS) AF: 0.853 AC: 72856 AN: 85402

European-Finnish (FIN) AF: 0.726 AC: 36962 AN: 50916

Middle Eastern (MID) AF: 0.766 AC: 4405 AN: 5748

European-Non Finnish (NFE) AF: 0.676 AC: 750686 AN: 1110020

Other (OTH) AF: 0.731 AC: 43905 AN: 60094

GnomAD4 genome AF: 0.762 AC: 115904 AN: 152188 Hom.: 44840 Cov.: 33 AF XY: 0.764 AC XY: 56812 AN XY: 74396

African (AFR) AF: 0.883 AC: 36684 AN: 41562

American (AMR) AF: 0.751 AC: 11482 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2820 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4213 AN: 5138

South Asian (SAS) AF: 0.853 AC: 4117 AN: 4828

European-Finnish (FIN) AF: 0.720 AC: 7621 AN: 10590

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46468 AN: 67998

Other (OTH) AF: 0.752 AC: 1587 AN: 2110

Alfa AF: 0.733 Hom.: 34479

Bravo AF: 0.770

Asia WGS AF: 0.850 AC: 2953 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.58
DANN	Benign	0.37
PhyloP100		-1.5
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: rs1549758; hg19: chr7-150695726; COSMIC: COSV52486190; COSMIC: COSV52486190;