rs9895453

Variant names:

• chr17-27783731-C-T
• rs9895453
• NM_000625.4:c.468-625G>A

Variant summary

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

The NM_000625.4(NOS2):​c.468-625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,092 control chromosomes in the GnomAD database, including 20,547 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 0.52 (20547 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.468-625G>A		intron_variant	Intron 5 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.468-625G>A		intron_variant	Intron 5 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78833 AN: 151972 Hom.: 20535 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.519 AC: 78891 AN: 152092 Hom.: 20547 Cov.: 33 AF XY: 0.523 AC XY: 38898 AN XY: 74350

African (AFR) AF: 0.500 AC: 20731 AN: 41478

American (AMR) AF: 0.547 AC: 8360 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2076 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2025 AN: 5174

South Asian (SAS) AF: 0.642 AC: 3099 AN: 4824

European-Finnish (FIN) AF: 0.549 AC: 5796 AN: 10564

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34912 AN: 67986

Other (OTH) AF: 0.536 AC: 1131 AN: 2112

Alfa AF: 0.516 Hom.: 6881

Bravo AF: 0.517

Asia WGS AF: 0.516 AC: 1798 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	0.082
DANN	Benign	0.50
PhyloP100		-1.8
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

Other links and lift over

dbSNP: rs9895453; hg19: chr17-26110757;