rs8068149

Variant names:

• chr17-27761829-G-A
• rs8068149
• NM_000625.4:c.2801-598C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-27761829-G-A
• chr17-27761829-G-C

Variant summary

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

The NM_000625.4(NOS2):​c.2801-598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,902 control chromosomes in the GnomAD database, including 18,506 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 0.49 (18506 hom., cov: 31)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 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.2801-598C>T		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.2801-598C>T		intron	N/A	ENSP00000327251.6	P35228-1
	NOS2	ENST00000886820.1		c.2801-598C>T		intron	N/A	ENSP00000556879.1
	NOS2	ENST00000646938.1		c.2798-598C>T		intron	N/A	ENSP00000494870.1	A0A2R8YDS4

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74048 AN: 151782 Hom.: 18471 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.488 AC: 74127 AN: 151902 Hom.: 18506 Cov.: 31 AF XY: 0.490 AC XY: 36410 AN XY: 74278

African (AFR) AF: 0.555 AC: 22984 AN: 41418

American (AMR) AF: 0.498 AC: 7597 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1677 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3286 AN: 5156

South Asian (SAS) AF: 0.596 AC: 2857 AN: 4796

European-Finnish (FIN) AF: 0.420 AC: 4441 AN: 10564

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29521 AN: 67918

Other (OTH) AF: 0.506 AC: 1066 AN: 2106

Alfa AF: 0.451 Hom.: 12638

Bravo AF: 0.493

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.5
DANN	Benign	0.77
PhyloP100		0.15
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: rs8068149; hg19: chr17-26088855;