dbSNP rs8192291: SOD3:p.Leu71Leu (chr4-24799732-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003102.4(SOD3):c.211C>T(p.Leu71Leu) 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

Publications

20 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SOD3	NM_003102.4 link	c.211C>T	p.Leu71Leu	synonymous_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2 link	n.306C>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4 link	c.211C>T	p.Leu71Leu	synonymous_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3
SOD3	ENST00000598411.1 link	c.*49C>T		downstream_gene_variant		5		ENSP00000472134.1

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

GnomAD2 exomes

AF:

0.196

AC:

31238

AN:

159278

AF XY:

0.197

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 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

African (AFR)

AF:

0.116

AC:

3774

AN:

32404

American (AMR)

AF:

0.164

AC:

6236

AN:

37976

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4564

AN:

25388

East Asian (EAS)

AF:

0.414

AC:

15300

AN:

36990

South Asian (SAS)

AF:

0.205

AC:

16730

AN:

81522

European-Finnish (FIN)

AF:

0.142

AC:

5653

AN:

39826

Middle Eastern (MID)

AF:

0.197

AC:

1126

AN:

5704

European-Non Finnish (NFE)

AF:

0.195

AC:

212954

AN:

1091224

Other (OTH)

AF:

0.194

AC:

11410

AN:

58710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

14845

29690

44534

59379

74224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7580

15160

22740

30320

37900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.172

AC:

26239

AN:

152136

Hom.:

2431

Cov.:

AF XY:

0.171

AC XY:

12690

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.118

AC:

4905

AN:

41540

American (AMR)

AF:

0.175

AC:

2677

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3472

East Asian (EAS)

AF:

0.364

AC:

1873

AN:

5146

South Asian (SAS)

AF:

0.209

AC:

1010

AN:

4824

European-Finnish (FIN)

AF:

0.132

AC:

1401

AN:

10616

Middle Eastern (MID)

AF:

0.199

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.192

AC:

13059

AN:

67934

Other (OTH)

AF:

0.187

AC:

394

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1137

2273

3410

4546

5683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.96

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over