rs2255929

Positions:

• chr17-27760941-T-A
• chr17-27760941-T-C

Variant summary

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

The NM_000625.4(NOS2):​c.2889-197A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,908 control chromosomes in the GnomAD database, including 19,184 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 0.50 (19184 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS2	NM_000625.4	c.2889-197A>T		intron_variant		ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.2889-197A>T		intron_variant		1	NM_000625.4	ENSP00000327251	P2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75257 AN: 151790 Hom.: 19150 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.423

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: 0.496 AC: 75333 AN: 151908 Hom.: 19184 Cov.: 32 AF XY: 0.498 AC XY: 36974 AN XY: 74214

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.506

Alfa AF: 0.462 Hom.: 2030

Bravo AF: 0.502

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	-0.87
CADD	Benign	0.48
DANN	Benign	0.79

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: rs2255929; hg19: chr17-26087967;