17-27782545-C-T

Position:

• chr17-27782545-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.630+399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,046 control chromosomes in the GnomAD database, including 14,632 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 0.43 (14632 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

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]

NOS2 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS2	NM_000625.4	c.630+399G>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.630+399G>A		intron_variant		1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66054 AN: 151928 Hom.: 14604 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.435 AC: 66130 AN: 152046 Hom.: 14632 Cov.: 32 AF XY: 0.435 AC XY: 32295 AN XY: 74312

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.458

Alfa AF: 0.395 Hom.: 16973

Bravo AF: 0.442

Asia WGS AF: 0.363 AC: 1264 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	0.31
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: rs944725; hg19: chr17-26109571;