rs9895453

Positions:

• chr17-27783731-C-T

Variant summary

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

The NM_000625.4(NOS2):​c.468-625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,092 control chromosomes in the GnomAD database, including 20,547 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 0.52 (20547 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.468-625G>A		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.468-625G>A		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78833 AN: 151972 Hom.: 20535 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.519 AC: 78891 AN: 152092 Hom.: 20547 Cov.: 33 AF XY: 0.523 AC XY: 38898 AN XY: 74350

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.536

Alfa AF: 0.513 Hom.: 4077

Bravo AF: 0.517

Asia WGS AF: 0.516 AC: 1798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.082
DANN	Benign	0.50

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: rs9895453; hg19: chr17-26110757;