17-27800492-C-G

Variant names:

• chr17-27800492-C-G
• rs10459953
• NM_000625.4:c.-227G>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.-227G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,062 control chromosomes in the GnomAD database, including 34,244 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 0.67 (34226 hom., cov: 31)
  • Exomes 𝑓: 0.68 (18 hom.)
• Consequence: NOS2 NM_000625.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 34 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)

ENSG00000266202 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	NM_000625.4	MANE Select	c.-227G>C		5_prime_UTR	Exon 1 of 27	NP_000616.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	ENST00000313735.11	TSL:1 MANE Select	c.-227G>C		5_prime_UTR	Exon 1 of 27	ENSP00000327251.6
	ENSG00000266202	ENST00000582441.1	TSL:4	c.439-1610G>C		intron	N/A	ENSP00000462879.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101783 AN: 151876 Hom.: 34191 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.674

GnomAD4 exome AF: 0.676 AC: 46 AN: 68 Hom.: 18 Cov.: 0 AF XY: 0.690 AC XY: 40 AN XY: 58

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.625 AC: 35 AN: 56

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.670 AC: 101870 AN: 151994 Hom.: 34226 Cov.: 31 AF XY: 0.673 AC XY: 50004 AN XY: 74290

African (AFR) AF: 0.695 AC: 28785 AN: 41436

American (AMR) AF: 0.724 AC: 11051 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2714 AN: 3468

East Asian (EAS) AF: 0.523 AC: 2705 AN: 5168

South Asian (SAS) AF: 0.720 AC: 3467 AN: 4812

European-Finnish (FIN) AF: 0.642 AC: 6780 AN: 10556

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 44008 AN: 67976

Other (OTH) AF: 0.674 AC: 1419 AN: 2106

Alfa AF: 0.459 Hom.: 905

Bravo AF: 0.676

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.43
PhyloP100		0.40
PromoterAI		-0.024	Neutral
Mutation Taster		=300/0	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: rs10459953; hg19: chr17-26127518;