rs12944039

chr17-27777738-G-A

Variant summary

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

The NM_000625.4(NOS2):c.1281+952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,090 control chromosomes in the GnomAD database, including 3,920 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 0.23 (3920 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.1281+952C>T		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.1281+952C>T		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34498 AN: 151972 Hom.: 3919 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.227 AC: 34511 AN: 152090 Hom.: 3920 Cov.: 32 AF XY: 0.228 AC XY: 16990 AN XY: 74358

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.238

Alfa AF: 0.227 Hom.: 1851

Bravo AF: 0.227

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	6.3
Dann	Benign	0.74

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: rs12944039; hg19: chr17-26104764; COSMIC: COSV58222519;