chr17-27789870-C-A

Variant names:

• chr17-27789870-C-A
• rs2072324
• NM_000625.4:c.111-182G>T

Variant summary

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

The NM_000625.4(NOS2):​c.111-182G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,170 control chromosomes in the GnomAD database, including 2,973 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 0.19 (2973 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.111-182G>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.111-182G>T		intron_variant	Intron 2 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28777 AN: 152052 Hom.: 2967 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.189 AC: 28792 AN: 152170 Hom.: 2973 Cov.: 32 AF XY: 0.190 AC XY: 14146 AN XY: 74390

African (AFR) AF: 0.113 AC: 4702 AN: 41540

American (AMR) AF: 0.271 AC: 4138 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3468

East Asian (EAS) AF: 0.209 AC: 1083 AN: 5170

South Asian (SAS) AF: 0.162 AC: 779 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10596

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14337 AN: 67984

Other (OTH) AF: 0.210 AC: 443 AN: 2110

Alfa AF: 0.134 Hom.: 327

Bravo AF: 0.193

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		-0.29
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: rs2072324; hg19: chr17-26116896; COSMIC: COSV107379315;