rs11080344

Positions:

• chr17-27777485-T-C
• chr17-27777485-T-G

Variant summary

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

The NM_000625.4(NOS2):​c.1281+1205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,096 control chromosomes in the GnomAD database, including 25,840 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 0.57 (25840 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1281+1205A>G		intron_variant		ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1281+1205A>G		intron_variant		1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85947 AN: 151982 Hom.: 25785 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.566 AC: 86050 AN: 152096 Hom.: 25840 Cov.: 32 AF XY: 0.568 AC XY: 42180 AN XY: 74324

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.552

Alfa AF: 0.474 Hom.: 25914

Bravo AF: 0.578

Asia WGS AF: 0.628 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
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: rs11080344; hg19: chr17-26104511;