rs9282801

Variant names:

• chr17-27769447-C-A
• rs9282801
• NM_000625.4:c.1859+88G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000625.4(NOS2):​c.1859+88G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,117,100 control chromosomes in the GnomAD database, including 62,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7966 hom., cov: 32)
  • Exomes 𝑓: 0.33 (54765 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.343
• Publications: 17 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-27769447-C-A is Benign according to our data. Variant chr17-27769447-C-A is described in ClinVar as Benign. ClinVar VariationId is 2688094.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 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.1859+88G>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.1859+88G>T		intron	N/A	ENSP00000327251.6	P35228-1
	NOS2	ENST00000886820.1		c.1859+88G>T		intron	N/A	ENSP00000556879.1
	NOS2	ENST00000646938.1		c.1856+88G>T		intron	N/A	ENSP00000494870.1	A0A2R8YDS4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48699 AN: 151842 Hom.: 7955 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.331 AC: 319125 AN: 965138 Hom.: 54765 AF XY: 0.335 AC XY: 167419 AN XY: 500476

African (AFR) AF: 0.264 AC: 6299 AN: 23888

American (AMR) AF: 0.238 AC: 10262 AN: 43172

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 9881 AN: 22520

East Asian (EAS) AF: 0.174 AC: 6521 AN: 37402

South Asian (SAS) AF: 0.361 AC: 27095 AN: 74990

European-Finnish (FIN) AF: 0.304 AC: 16077 AN: 52910

Middle Eastern (MID) AF: 0.466 AC: 1500 AN: 3216

European-Non Finnish (NFE) AF: 0.342 AC: 226722 AN: 663256

Other (OTH) AF: 0.337 AC: 14768 AN: 43784

GnomAD4 genome AF: 0.321 AC: 48749 AN: 151962 Hom.: 7966 Cov.: 32 AF XY: 0.321 AC XY: 23842 AN XY: 74282

African (AFR) AF: 0.267 AC: 11086 AN: 41458

American (AMR) AF: 0.288 AC: 4401 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1046 AN: 5154

South Asian (SAS) AF: 0.366 AC: 1765 AN: 4824

European-Finnish (FIN) AF: 0.305 AC: 3216 AN: 10558

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24201 AN: 67940

Other (OTH) AF: 0.365 AC: 767 AN: 2104

Alfa AF: 0.337 Hom.: 3642

Bravo AF: 0.315

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.77
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9282801; hg19: chr17-26096473; COSMIC: COSV58227209;