chr17-27789822-C-T

Position:

• chr17-27789822-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.111-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 626,992 control chromosomes in the GnomAD database, including 46,985 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 0.34 (10002 hom., cov: 32)
  • Exomes 𝑓: 0.37 (36983 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS2	NM_000625.4	c.111-134G>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.111-134G>A		intron_variant		1	NM_000625.4	ENSP00000327251	P2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52088 AN: 151982 Hom.: 10003 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.373 AC: 177142 AN: 474892 Hom.: 36983 AF XY: 0.365 AC XY: 92495 AN XY: 253096

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.0507

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.342 AC: 52089 AN: 152100 Hom.: 10002 Cov.: 32 AF XY: 0.337 AC XY: 25065 AN XY: 74330

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.0723

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.337

Alfa AF: 0.415 Hom.: 19989

Bravo AF: 0.327

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.10
DANN	Benign	0.61

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: rs8072199; hg19: chr17-26116848;