Genetic Variant SOD2:c.93-416C>G (chr6-159693279-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000545162.5(SOD2):c.93-416C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 983,860 control chromosomes in the GnomAD database, including 28,464 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 0.23 ( 4223 hom., cov: 28)

Exomes 𝑓: 0.24 ( 24241 hom. )

Consequence

SOD2
ENST00000545162.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.653

Publications

23 publications found

Variant links:

Genes affected

SOD2 (HGNC:11180): (superoxide dismutase 2) This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

SOD2 Gene-Disease associations (from GenCC):

cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SOD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.-112C>G		upstream_gene_variant		ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7 link	c.-112C>G		upstream_gene_variant		1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

34604

AN:

149370

Hom.:

4220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.0324

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.394

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.238

GnomAD4 exome

AF:

0.236

AC:

196881

AN:

834382

Hom.:

24241

Cov.:

AF XY:

0.238

AC XY:

102128

AN XY:

428674

show subpopulations

African (AFR)

AF:

0.179

AC:

3082

AN:

17244

American (AMR)

AF:

0.204

AC:

5274

AN:

25844

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

3937

AN:

19392

East Asian (EAS)

AF:

0.373

AC:

9322

AN:

24970

South Asian (SAS)

AF:

0.254

AC:

15510

AN:

61168

European-Finnish (FIN)

AF:

0.312

AC:

11091

AN:

35600

Middle Eastern (MID)

AF:

0.284

AC:

838

AN:

2948

European-Non Finnish (NFE)

AF:

0.228

AC:

138976

AN:

609394

Other (OTH)

AF:

0.234

AC:

8851

AN:

37822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

6781

13562

20343

27124

33905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3834

7668

11502

15336

19170

<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:

0.232

AC:

34619

AN:

149478

Hom.:

4223

Cov.:

AF XY:

0.238

AC XY:

17375

AN XY:

72960

show subpopulations

African (AFR)

AF:

0.188

AC:

7674

AN:

40900

American (AMR)

AF:

0.228

AC:

3434

AN:

15090

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

697

AN:

3454

East Asian (EAS)

AF:

0.394

AC:

1964

AN:

4986

South Asian (SAS)

AF:

0.270

AC:

1296

AN:

4794

European-Finnish (FIN)

AF:

0.332

AC:

3252

AN:

9804

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.234

AC:

15716

AN:

67178

Other (OTH)

AF:

0.237

AC:

494

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

Heterozygous variant carriers

1143

2285

3428

4570

5713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.116

Hom.:

195

Bravo

AF:

0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.4

(source)

DANN

Benign

0.24

PhyloP100

-0.65

PromoterAI

0.17

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

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

Computational scores

Splicing

Publications

Other links and lift over