rs28998802

Variant names:

• chr17-27797882-G-A
• rs28998802
• NM_000625.4:c.110+818C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-27797882-G-A
• chr17-27797882-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000625.4(NOS2):​c.110+818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,102 control chromosomes in the GnomAD database, including 1,268 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 0.11 (1268 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.110+818C>T		intron_variant	Intron 2 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.110+818C>T		intron_variant	Intron 2 of 26	1	NM_000625.4	ENSP00000327251.6
NOS2	ENST00000697337.1	n.110+818C>T		intron_variant	Intron 1 of 23			ENSP00000513259.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16963 AN: 151984 Hom.: 1265 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.112 AC: 16981 AN: 152102 Hom.: 1268 Cov.: 32 AF XY: 0.115 AC XY: 8548 AN XY: 74338

African (AFR) AF: 0.0297 AC: 1232 AN: 41508

American (AMR) AF: 0.149 AC: 2284 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3466

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5176

South Asian (SAS) AF: 0.185 AC: 893 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2046 AN: 10560

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9680 AN: 67972

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.101 Hom.: 264

Bravo AF: 0.102

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs28998802; hg19: chr17-26124908;