17-27776964-C-T

Variant names:

• chr17-27776964-C-T
• rs17718148
• NM_000625.4:c.1281+1726G>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.1281+1726G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,086 control chromosomes in the GnomAD database, including 2,598 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 0.18 (2598 hom., cov: 31)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.11
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 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.1281+1726G>A		intron	N/A	NP_000616.3	P35228-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	ENST00000313735.11	TSL:1 MANE Select	c.1281+1726G>A		intron	N/A	ENSP00000327251.6	P35228-1
	NOS2	ENST00000886820.1		c.1281+1726G>A		intron	N/A	ENSP00000556879.1
	NOS2	ENST00000646938.1		c.1278+1726G>A		intron	N/A	ENSP00000494870.1	A0A2R8YDS4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27360 AN: 151968 Hom.: 2600 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.180 AC: 27366 AN: 152086 Hom.: 2598 Cov.: 31 AF XY: 0.180 AC XY: 13396 AN XY: 74318

African (AFR) AF: 0.132 AC: 5485 AN: 41478

American (AMR) AF: 0.181 AC: 2763 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3468

East Asian (EAS) AF: 0.145 AC: 747 AN: 5164

South Asian (SAS) AF: 0.179 AC: 862 AN: 4814

European-Finnish (FIN) AF: 0.193 AC: 2041 AN: 10578

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13608 AN: 67988

Other (OTH) AF: 0.204 AC: 430 AN: 2106

Alfa AF: 0.174 Hom.: 331

Bravo AF: 0.179

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.023
DANN	Benign	0.39
PhyloP100		-4.1
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: rs17718148; hg19: chr17-26103990;