17-27763728-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.2592+253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,150 control chromosomes in the GnomAD database, including 34,632 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 0.67 (34632 hom., cov: 28)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.2592+253A>G		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.2592+253A>G		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 101667 AN: 151042 Hom.: 34583 Cov.: 28

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.673 AC: 101772 AN: 151150 Hom.: 34632 Cov.: 28 AF XY: 0.677 AC XY: 49938 AN XY: 73814

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.690

Alfa AF: 0.636 Hom.: 3130

Bravo AF: 0.676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.2
Dann	Benign	0.78

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: rs2297510; hg19: chr17-26090754;