rs8068149

Positions:

• chr17-27761829-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000625.4(NOS2):​c.2801-598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,902 control chromosomes in the GnomAD database, including 18,506 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 0.49 (18506 hom., cov: 31)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.2801-598C>T		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.2801-598C>T		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74048 AN: 151782 Hom.: 18471 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74127 AN: 151902 Hom.: 18506 Cov.: 31 AF XY: 0.490 AC XY: 36410 AN XY: 74278

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.506

Alfa AF: 0.451 Hom.: 10639

Bravo AF: 0.493

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.5
DANN	Benign	0.77

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: rs8068149; hg19: chr17-26088855;