chr17-27770105-T-C

Variant names:

• chr17-27770105-T-C
• rs9797244
• NM_000625.4:c.1810-521A>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.1810-521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,204 control chromosomes in the GnomAD database, including 2,811 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 (2811 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 19 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1810-521A>G		intron_variant	Intron 15 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1810-521A>G		intron_variant	Intron 15 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28900 AN: 152086 Hom.: 2810 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.190 AC: 28916 AN: 152204 Hom.: 2811 Cov.: 33 AF XY: 0.191 AC XY: 14182 AN XY: 74432

African (AFR) AF: 0.193 AC: 7995 AN: 41510

American (AMR) AF: 0.173 AC: 2642 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3470

East Asian (EAS) AF: 0.153 AC: 792 AN: 5188

South Asian (SAS) AF: 0.172 AC: 831 AN: 4828

European-Finnish (FIN) AF: 0.186 AC: 1964 AN: 10582

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12875 AN: 68014

Other (OTH) AF: 0.210 AC: 444 AN: 2114

Alfa AF: 0.189 Hom.: 9434

Bravo AF: 0.191

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.64
PhyloP100		0.32
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: rs9797244; hg19: chr17-26097131;