rs753482

Variant names:

• chr7-151009295-C-A
• rs753482
• NM_000603.5:c.2324+28C>A

Your query was ambiguous. Multiple possible variants found:

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

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.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 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.89
• Publications: 25 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=-0.89).
• BP6: Variant 7-151009295-C-A is Benign according to our data. Variant chr7-151009295-C-A is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.2324+28C>A		intron_variant	Intron 19 of 26	ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.2324+28C>A		intron_variant	Intron 19 of 26	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000461406.5	c.1706+28C>A		intron_variant	Intron 16 of 23	2		ENSP00000417143.1
NOS3	ENST00000475017.1	c.203+28C>A		intron_variant	Intron 2 of 6	2		ENSP00000418245.1
NOS3	ENST00000473057.1	n.268+28C>A		intron_variant	Intron 2 of 2	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

GnomAD2 exomes AF: 0.832 AC: 189230 AN: 227524 AF XY: 0.831

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 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

African (AFR) AF: 0.712 AC: 23162 AN: 32530

American (AMR) AF: 0.860 AC: 36361 AN: 42276

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 19289 AN: 25138

East Asian (EAS) AF: 0.970 AC: 37039 AN: 38170

South Asian (SAS) AF: 0.870 AC: 72663 AN: 83494

European-Finnish (FIN) AF: 0.843 AC: 42857 AN: 50830

Middle Eastern (MID) AF: 0.794 AC: 4452 AN: 5606

European-Non Finnish (NFE) AF: 0.789 AC: 840836 AN: 1066194

Other (OTH) AF: 0.795 AC: 46134 AN: 58062

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

African (AFR) AF: 0.702 AC: 26304 AN: 37488

American (AMR) AF: 0.770 AC: 10246 AN: 13308

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2442 AN: 3184

East Asian (EAS) AF: 0.947 AC: 4093 AN: 4322

South Asian (SAS) AF: 0.838 AC: 3375 AN: 4026

European-Finnish (FIN) AF: 0.827 AC: 6790 AN: 8208

Middle Eastern (MID) AF: 0.713 AC: 184 AN: 258

European-Non Finnish (NFE) AF: 0.765 AC: 46817 AN: 61188

Other (OTH) AF: 0.746 AC: 1388 AN: 1860

Alfa AF: 0.789 Hom.: 45793

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 12716763, 24302629, 18349107) -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-2.9
PromoterAI		-0.045	Neutral
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: rs753482; hg19: chr7-150706383;