rs3730014

chr17-27798717-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_000625.4(NOS2):c.93C>T(p.Ala31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,612,452 control chromosomes in the GnomAD database, including 308 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 0.012 (33 hom., cov: 32)
  • Exomes 𝑓: 0.016 (275 hom.)
• Consequence: NOS2 NM_000625.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.622 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0123 (1874/152290) while in subpopulation SAS AF= 0.0392 (189/4824). AF 95% confidence interval is 0.0346. There are 33 homozygotes in gnomad4. There are 958 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4	c.93C>T	p.Ala31=	synonymous_variant	2/27	ENST00000313735.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS2	ENST00000313735.11	c.93C>T	p.Ala31=	synonymous_variant	2/27	1	NM_000625.4	P2
NOS2	ENST00000697337.1	c.93C>T	p.Ala31=	synonymous_variant, NMD_transcript_variant	1/24

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1872 AN: 152172 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0159 AC: 4002 AN: 251420 Hom.: 55 AF XY: 0.0177 AC XY: 2402 AN XY: 135896

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00477

Gnomad ASJ exome AF: 0.0369

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0390

Gnomad FIN exome AF: 0.0147

Gnomad NFE exome AF: 0.0160

Gnomad OTH exome AF: 0.0140

GnomAD4 exome AF: 0.0156 AC: 22775 AN: 1460162 Hom.: 275 Cov.: 31 AF XY: 0.0165 AC XY: 12022 AN XY: 726484

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.00487

Gnomad4 ASJ exome AF: 0.0372

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0392

Gnomad4 FIN exome AF: 0.0156

Gnomad4 NFE exome AF: 0.0146

Gnomad4 OTH exome AF: 0.0156

GnomAD4 genome AF: 0.0123 AC: 1874 AN: 152290 Hom.: 33 Cov.: 32 AF XY: 0.0129 AC XY: 958 AN XY: 74464

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.00745

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0392

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0157 Hom.: 12

Bravo AF: 0.0100

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0193

EpiControl AF: 0.0177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.9
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs3730014; hg19: chr17-26125743;