rs753482

Positions:

• chr7-151009295-C-A
• chr7-151009295-C-G
• chr7-151009295-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000297494.8(NOS3):​c.2324+28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,536,942 control chromosomes in the GnomAD database, including 489,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (38876 hom., cov: 21)
  • Exomes 𝑓: 0.80 (450567 hom.)
• Consequence: NOS3 ENST00000297494.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.89

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-151009295-C-A is Benign according to our data. Variant chr7-151009295-C-A is described in ClinVar as [Benign]. Clinvar id is 1261436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.2324+28C>A		intron_variant		ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.2324+28C>A		intron_variant		1	NM_000603.5	ENSP00000297494	P1
NOS3	ENST00000461406.5	c.1706+28C>A		intron_variant		2		ENSP00000417143
NOS3	ENST00000475017.1	c.205+28C>A		intron_variant		2		ENSP00000418245
NOS3	ENST00000473057.1	n.268+28C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.760 AC: 102210 AN: 134530 Hom.: 38849 Cov.: 21

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.721

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.745

GnomAD3 exomes AF: 0.832 AC: 189230 AN: 227524 Hom.: 78922 AF XY: 0.831 AC XY: 102104 AN XY: 122802

Gnomad AFR exome AF: 0.725

Gnomad AMR exome AF: 0.870

Gnomad ASJ exome AF: 0.777

Gnomad EAS exome AF: 0.963

Gnomad SAS exome AF: 0.875

Gnomad FIN exome AF: 0.855

Gnomad NFE exome AF: 0.802

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.801 AC: 1122793 AN: 1402300 Hom.: 450567 Cov.: 25 AF XY: 0.802 AC XY: 560017 AN XY: 698088

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.767

Gnomad4 EAS exome AF: 0.970

Gnomad4 SAS exome AF: 0.870

Gnomad4 FIN exome AF: 0.843

Gnomad4 NFE exome AF: 0.789

Gnomad4 OTH exome AF: 0.795

GnomAD4 genome AF: 0.760 AC: 102293 AN: 134642 Hom.: 38876 Cov.: 21 AF XY: 0.764 AC XY: 49733 AN XY: 65110

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.746

Alfa AF: 0.788 Hom.: 36120

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	This variant is associated with the following publications: (PMID: 12716763, 24302629, 18349107) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs753482; hg19: chr7-150706383;