17-27777084-C-G

Variant names:

• chr17-27777084-C-G
• rs2314810
• NM_000625.4:c.1281+1606G>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.1281+1606G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 152,270 control chromosomes in the GnomAD database, including 68,548 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 0.95 (68548 hom., cov: 31)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 16 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1281+1606G>C		intron_variant	Intron 11 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1281+1606G>C		intron_variant	Intron 11 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144131 AN: 152152 Hom.: 68483 Cov.: 31

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.947 AC: 144254 AN: 152270 Hom.: 68548 Cov.: 31 AF XY: 0.945 AC XY: 70334 AN XY: 74450

African (AFR) AF: 0.986 AC: 40971 AN: 41564

American (AMR) AF: 0.933 AC: 14274 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3196 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3684 AN: 5158

South Asian (SAS) AF: 0.897 AC: 4323 AN: 4818

European-Finnish (FIN) AF: 0.949 AC: 10076 AN: 10612

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64630 AN: 68024

Other (OTH) AF: 0.927 AC: 1960 AN: 2114

Alfa AF: 0.964 Hom.: 3313

Bravo AF: 0.946

Asia WGS AF: 0.840 AC: 2923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.57
PhyloP100		0.064
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: rs2314810; hg19: chr17-26104110;