chr17-27765011-C-T

Variant names:

• chr17-27765011-C-T
• rs944722
• NM_000625.4:c.2428+524G>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.2428+524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 151,946 control chromosomes in the GnomAD database, including 35,158 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 0.68 (35158 hom., cov: 31)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 24 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.2428+524G>A		intron_variant	Intron 20 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.2428+524G>A		intron_variant	Intron 20 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102475 AN: 151828 Hom.: 35104 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.675 AC: 102590 AN: 151946 Hom.: 35158 Cov.: 31 AF XY: 0.678 AC XY: 50330 AN XY: 74244

African (AFR) AF: 0.780 AC: 32314 AN: 41440

American (AMR) AF: 0.663 AC: 10115 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2378 AN: 3466

East Asian (EAS) AF: 0.690 AC: 3564 AN: 5166

South Asian (SAS) AF: 0.834 AC: 4014 AN: 4812

European-Finnish (FIN) AF: 0.592 AC: 6247 AN: 10552

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41567 AN: 67928

Other (OTH) AF: 0.691 AC: 1457 AN: 2110

Alfa AF: 0.623 Hom.: 67768

Bravo AF: 0.678

Asia WGS AF: 0.773 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.78
PhyloP100		0.30
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: rs944722; hg19: chr17-26092037;