dbSNP rs4342445: SOD2:c.*5303C>T (chr6-159677190-G-A) – 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.*5303C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,138 control chromosomes in the GnomAD database, including 4,006 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 0.22 ( 4005 hom., cov: 32)

Exomes 𝑓: 0.29 ( 1 hom. )

Consequence

SOD2
NM_000636.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.295

Publications

29 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.*5303C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7 link	c.*5303C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_000636.4	ENSP00000446252.1		P04179-1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33800

AN:

152006

Hom.:

4001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.230

GnomAD4 exome

AF:

0.286

AC:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.222

AC:

33818

AN:

152124

Hom.:

4005

Cov.:

AF XY:

0.230

AC XY:

17073

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.149

AC:

6189

AN:

41514

American (AMR)

AF:

0.237

AC:

3628

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

696

AN:

3470

East Asian (EAS)

AF:

0.402

AC:

2078

AN:

5174

South Asian (SAS)

AF:

0.272

AC:

1309

AN:

4810

European-Finnish (FIN)

AF:

0.329

AC:

3469

AN:

10556

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.233

AC:

15872

AN:

68002

Other (OTH)

AF:

0.229

AC:

484

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1335

2670

4004

5339

6674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.231

Hom.:

8272

Bravo

AF:

0.213

Asia WGS

AF:

0.304

AC:

1056

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.53

PhyloP100

-0.29

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