dbSNP rs5746094: SOD2:c.23+9A>G (chr6-159693136-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000636.4(SOD2):c.23+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,529,256 control chromosomes in the GnomAD database, including 45,599 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 ( 4232 hom., cov: 31)

Exomes 𝑓: 0.24 ( 41367 hom. )

Consequence

SOD2
NM_000636.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.203

Publications

15 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=-0.6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.23+9A>G		intron_variant	Intron 1 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7 link	c.23+9A>G		intron_variant	Intron 1 of 4	1	NM_000636.4	ENSP00000446252.1		P04179-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35168

AN:

151666

Hom.:

4230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.238

GnomAD2 exomes

AF:

0.247

AC:

32795

AN:

132636

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.381

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.242

AC:

333911

AN:

1377482

Hom.:

41367

Cov.:

AF XY:

0.244

AC XY:

165871

AN XY:

679418

show subpopulations

African (AFR)

AF:

0.180

AC:

5224

AN:

28956

American (AMR)

AF:

0.209

AC:

7035

AN:

33720

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5026

AN:

24464

East Asian (EAS)

AF:

0.376

AC:

12492

AN:

33210

South Asian (SAS)

AF:

0.258

AC:

19891

AN:

76978

European-Finnish (FIN)

AF:

0.313

AC:

15036

AN:

48012

Middle Eastern (MID)

AF:

0.284

AC:

1265

AN:

4458

European-Non Finnish (NFE)

AF:

0.237

AC:

254193

AN:

1070624

Other (OTH)

AF:

0.241

AC:

13749

AN:

57060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

12770

25539

38309

51078

63848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8832

17664

26496

35328

44160

<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:

35182

AN:

151774

Hom.:

4232

Cov.:

AF XY:

0.239

AC XY:

17694

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.188

AC:

7777

AN:

41422

American (AMR)

AF:

0.227

AC:

3461

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

700

AN:

3464

East Asian (EAS)

AF:

0.397

AC:

2031

AN:

5122

South Asian (SAS)

AF:

0.270

AC:

1303

AN:

4820

European-Finnish (FIN)

AF:

0.329

AC:

3458

AN:

10516

Middle Eastern (MID)

AF:

0.212

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.234

AC:

15859

AN:

67840

Other (OTH)

AF:

0.237

AC:

501

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1392

2783

4175

5566

6958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.232

Hom.:

3625

Bravo

AF:

0.223

Asia WGS

AF:

0.301

AC:

1039

AN:

3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.8

(source)

DANN

Benign

0.43

PhyloP100

0.20

PromoterAI

0.017

Neutral

(source)

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