rs6505469

Positions:

• chr17-27784860-T-A
• chr17-27784860-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.468-1754A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,038 control chromosomes in the GnomAD database, including 30,225 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 0.62 (30225 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.468-1754A>T		intron_variant		ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.468-1754A>T		intron_variant		1	NM_000625.4	P2

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94017 AN: 151920 Hom.: 30161 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.619 AC: 94148 AN: 152038 Hom.: 30225 Cov.: 32 AF XY: 0.622 AC XY: 46229 AN XY: 74324

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.606

Alfa AF: 0.571 Hom.: 3047

Bravo AF: 0.629

Asia WGS AF: 0.561 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.58

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: rs6505469; hg19: chr17-26111886;