rs8072199

Variant names:

• chr17-27789822-C-T
• rs8072199
• NM_000625.4:c.111-134G>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.111-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 626,992 control chromosomes in the GnomAD database, including 46,985 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 0.34 (10002 hom., cov: 32)
  • Exomes 𝑓: 0.37 (36983 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 32 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.111-134G>A		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.111-134G>A		intron_variant	Intron 2 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52088 AN: 151982 Hom.: 10003 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.373 AC: 177142 AN: 474892 Hom.: 36983 AF XY: 0.365 AC XY: 92495 AN XY: 253096

African (AFR) AF: 0.214 AC: 2878 AN: 13468

American (AMR) AF: 0.242 AC: 6323 AN: 26134

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 5532 AN: 14388

East Asian (EAS) AF: 0.0507 AC: 1482 AN: 29248

South Asian (SAS) AF: 0.215 AC: 10935 AN: 50796

European-Finnish (FIN) AF: 0.440 AC: 14968 AN: 34056

Middle Eastern (MID) AF: 0.239 AC: 710 AN: 2970

European-Non Finnish (NFE) AF: 0.450 AC: 124928 AN: 277588

Other (OTH) AF: 0.358 AC: 9386 AN: 26244

GnomAD4 genome AF: 0.342 AC: 52089 AN: 152100 Hom.: 10002 Cov.: 32 AF XY: 0.337 AC XY: 25065 AN XY: 74330

African (AFR) AF: 0.216 AC: 8952 AN: 41490

American (AMR) AF: 0.285 AC: 4366 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1361 AN: 3472

East Asian (EAS) AF: 0.0723 AC: 374 AN: 5170

South Asian (SAS) AF: 0.207 AC: 998 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4687 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30108 AN: 67966

Other (OTH) AF: 0.337 AC: 712 AN: 2112

Alfa AF: 0.412 Hom.: 27048

Bravo AF: 0.327

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.10
DANN	Benign	0.61
PhyloP100		-1.6
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: rs8072199; hg19: chr17-26116848;