Variant rs8192291 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003102.4(SOD3):c.211C>T(p.Leu71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,561,880 control chromosomes in the GnomAD database, including 30,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2431 hom., cov: 33)

Exomes 𝑓: 0.20 ( 28500 hom. )

Consequence

SOD3
NM_003102.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

SOD3 (HGNC:11181): (superoxide dismutase 3) This gene encodes a member of the superoxide dismutase (SOD) protein family. SODs are antioxidant enzymes that catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen, which may protect the brain, lungs, and other tissues from oxidative stress. Proteolytic processing of the encoded protein results in the formation of two distinct homotetramers that differ in their ability to interact with the extracellular matrix (ECM). Homotetramers consisting of the intact protein, or type C subunit, exhibit high affinity for heparin and are anchored to the ECM. Homotetramers consisting of a proteolytically cleaved form of the protein, or type A subunit, exhibit low affinity for heparin and do not interact with the ECM. A mutation in this gene may be associated with increased heart disease risk. [provided by RefSeq, Oct 2015]

SOD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-24799732-C-T is Benign according to our data. Variant chr4-24799732-C-T is described in ClinVar as [Benign]. Clinvar id is 3060611.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD3	NM_003102.4 linkuse as main transcript	c.211C>T	p.Leu71=	synonymous_variant	2/2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 linkuse as main transcript	n.306C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4 linkuse as main transcript	c.211C>T	p.Leu71=	synonymous_variant	2/2	1	NM_003102.4	ENSP00000371554	P1
SOD3	ENST00000598411.1 linkuse as main transcript			downstream_gene_variant		5		ENSP00000472134

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26238

AN:

152022

Hom.:

2428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.196

AC:

31238

AN:

159278

Hom.:

3229

AF XY:

0.197

AC XY:

17459

AN XY:

88404

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.197

AC:

277747

AN:

1409744

Hom.:

28500

Cov.:

AF XY:

0.198

AC XY:

137862

AN XY:

698034

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.414

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.172

AC:

26239

AN:

152136

Hom.:

2431

Cov.:

AF XY:

0.171

AC XY:

12690

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.364

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.179

Hom.:

553

Bravo

AF:

0.175

Asia WGS

AF:

0.257

AC:

891

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SOD3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.7

DANN

Benign

0.96

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over