chr17-27797673-T-C

Variant names:

• chr17-27797673-T-C
• rs16949
• NM_000625.4:c.110+1027A>G

Variant summary

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

The NM_000625.4(NOS2):​c.110+1027A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,178 control chromosomes in the GnomAD database, including 3,830 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 0.22 (3830 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.110+1027A>G		intron_variant	Intron 2 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.110+1027A>G		intron_variant	Intron 2 of 26	1	NM_000625.4	ENSP00000327251.6
NOS2	ENST00000697337.1	n.110+1027A>G		intron_variant	Intron 1 of 23			ENSP00000513259.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33541 AN: 152060 Hom.: 3830 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.220 AC: 33547 AN: 152178 Hom.: 3830 Cov.: 33 AF XY: 0.219 AC XY: 16317 AN XY: 74376

African (AFR) AF: 0.201 AC: 8348 AN: 41512

American (AMR) AF: 0.190 AC: 2910 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3468

East Asian (EAS) AF: 0.168 AC: 869 AN: 5174

South Asian (SAS) AF: 0.193 AC: 932 AN: 4824

European-Finnish (FIN) AF: 0.231 AC: 2441 AN: 10586

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16127 AN: 68000

Other (OTH) AF: 0.227 AC: 477 AN: 2104

Alfa AF: 0.222 Hom.: 966

Bravo AF: 0.219

Asia WGS AF: 0.151 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.59
PhyloP100		-0.093
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: rs16949; hg19: chr17-26124699;