17-27765011-C-T

Position:

• chr17-27765011-C-T

Variant summary

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

The ENST00000313735.11(NOS2):​c.2428+524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,946 control chromosomes in the GnomAD database, including 35,158 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 0.68 (35158 hom., cov: 31)
• Consequence: NOS2 ENST00000313735.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.89).
• 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	Protein	UniProt
NOS2	NM_000625.4	c.2428+524G>A		intron_variant		ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.2428+524G>A		intron_variant		1	NM_000625.4	ENSP00000327251	P2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102475 AN: 151828 Hom.: 35104 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.675 AC: 102590 AN: 151946 Hom.: 35158 Cov.: 31 AF XY: 0.678 AC XY: 50330 AN XY: 74244

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.691

Alfa AF: 0.625 Hom.: 22371

Bravo AF: 0.678

Asia WGS AF: 0.773 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
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: rs944722; hg19: chr17-26092037;