NM_000625.4:c.468-704A>T

Variant names:

• chr17-27783810-T-A
• rs17722851
• NM_000625.4:c.468-704A>T

Variant summary

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

The NM_000625.4(NOS2):​c.468-704A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,290 control chromosomes in the GnomAD database, including 930 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 0.10 (930 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 14 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.468-704A>T		intron_variant	Intron 5 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.468-704A>T		intron_variant	Intron 5 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15240 AN: 152170 Hom.: 924 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0730

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0812

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

GnomAD4 genome AF: 0.100 AC: 15264 AN: 152290 Hom.: 930 Cov.: 32 AF XY: 0.104 AC XY: 7753 AN XY: 74460

African (AFR) AF: 0.0480 AC: 1994 AN: 41560

American (AMR) AF: 0.111 AC: 1695 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 253 AN: 3468

East Asian (EAS) AF: 0.0623 AC: 323 AN: 5184

South Asian (SAS) AF: 0.221 AC: 1068 AN: 4828

European-Finnish (FIN) AF: 0.144 AC: 1527 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8139 AN: 68010

Other (OTH) AF: 0.0879 AC: 186 AN: 2116

Alfa AF: 0.112 Hom.: 124

Bravo AF: 0.0934

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.1
DANN	Benign	0.74
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17722851; hg19: chr17-26110836;