Variant 17-27798717-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.622

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS2	NM_000625.4 linkuse as main transcript	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 linkuse as main transcript	c.93C>T	p.Ala31=	synonymous_variant	2/27	1	NM_000625.4	P2	P35228-1
NOS2	ENST00000697337.1 linkuse as main transcript	c.93C>T	p.Ala31=	synonymous_variant, NMD_transcript_variant	1/24

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1872

AN:

152172

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0177

AC XY:

2402

AN XY:

135896

show subpopulations

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.:

AF XY:

0.0165

AC XY:

12022

AN XY:

726484

show subpopulations

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.:

Cov.:

AF XY:

0.0129

AC XY:

958

AN XY:

74464

show subpopulations

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.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.0120

AC:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over