chr17-27756664-G-C

Variant names:

• chr17-27756664-G-C
• rs7406657
• NM_000625.4:c.*582C>G

Variant summary

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

The NM_000625.4(NOS2):​c.*582C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,230 control chromosomes in the GnomAD database, including 4,609 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 0.24 (4608 hom., cov: 33)
  • Exomes 𝑓: 0.28 (1 hom.)
• Consequence: NOS2 NM_000625.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	NM_000625.4	MANE Select	c.*582C>G		downstream_gene	N/A	NP_000616.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	ENST00000313735.11	TSL:1 MANE Select	c.*582C>G		downstream_gene	N/A	ENSP00000327251.6
	NOS2	ENST00000886820.1		c.*582C>G		downstream_gene	N/A	ENSP00000556879.1
	NOS2	ENST00000646938.1		c.*582C>G		downstream_gene	N/A	ENSP00000494870.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36548 AN: 152052 Hom.: 4603 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.283 AC: 17 AN: 60 Hom.: 1 AF XY: 0.342 AC XY: 13 AN XY: 38

African (AFR) AF: 0.00 AC: 0 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: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 12 AN: 48

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

GnomAD4 genome AF: 0.240 AC: 36588 AN: 152170 Hom.: 4608 Cov.: 33 AF XY: 0.240 AC XY: 17885 AN XY: 74392

African (AFR) AF: 0.182 AC: 7552 AN: 41532

American (AMR) AF: 0.319 AC: 4881 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1513 AN: 5154

South Asian (SAS) AF: 0.353 AC: 1704 AN: 4826

European-Finnish (FIN) AF: 0.215 AC: 2274 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16798 AN: 67992

Other (OTH) AF: 0.269 AC: 568 AN: 2112

Alfa AF: 0.244 Hom.: 561

Bravo AF: 0.245

Asia WGS AF: 0.294 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.47
PhyloP100		-0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7406657; hg19: chr17-26083690;