rs16966563

Positions:

• chr17-27788923-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000625.4(NOS2):​c.204A>G​(p.Pro68Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,613,798 control chromosomes in the GnomAD database, including 1,993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.069 (811 hom., cov: 33)
  • Exomes 𝑓: 0.027 (1182 hom.)
• Consequence: NOS2 NM_000625.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

Genes affected

NOS2 (HGNC:7873): (nitric oxide synthase 2) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

NOS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.225 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS2	NM_000625.4	c.204A>G	p.Pro68Pro	synonymous_variant	4/27	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.204A>G	p.Pro68Pro	synonymous_variant	4/27	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10549 AN: 152152 Hom.: 810 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00734

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.00536

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0463

GnomAD3 exomes AF: 0.0372 AC: 9332 AN: 251182 Hom.: 483 AF XY: 0.0333 AC XY: 4521 AN XY: 135732

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.0628

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00979

Gnomad SAS exome AF: 0.0454

Gnomad FIN exome AF: 0.00508

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.0276

GnomAD4 exome AF: 0.0270 AC: 39398 AN: 1461528 Hom.: 1182 Cov.: 31 AF XY: 0.0268 AC XY: 19455 AN XY: 727024

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.0628

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.00592

Gnomad4 SAS exome AF: 0.0462

Gnomad4 FIN exome AF: 0.00543

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.0334

GnomAD4 genome AF: 0.0694 AC: 10567 AN: 152270 Hom.: 811 Cov.: 33 AF XY: 0.0680 AC XY: 5060 AN XY: 74464

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00755

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.00536

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0320 Hom.: 301

Bravo AF: 0.0783

Asia WGS AF: 0.0360 AC: 124 AN: 3478

EpiCase AF: 0.0173

EpiControl AF: 0.0188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.1
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs16966563; hg19: chr17-26115949;