dbSNP rs2758357: SOD2:c.92+13307G>A (chr6-159713959-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001322817.2(SOD2):c.-116+16926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 790,188 control chromosomes in the GnomAD database, including 67,318 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 0.40 ( 13691 hom., cov: 30)

Exomes 𝑓: 0.39 ( 53627 hom. )

Consequence

SOD2
NM_001322817.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0620

Publications

6 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 links:

HNRNPH1P1 (HGNC:48751): (heterogeneous nuclear ribonucleoprotein H1 pseudogene 1)

HNRNPH1P1 links:

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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=-0.65).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322817.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SOD2	NM_001322817.2	c.-116+16926G>A	intron	N/A	NP_001309746.1	P04179-4
SOD2	NM_001322819.2	c.-116+13307G>A	intron	N/A	NP_001309748.1	P04179-4
SOD2	NM_001322820.2	c.-116+12893G>A	intron	N/A	NP_001309749.1	P04179-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOD2	ENST00000545162.5	TSL:3	c.92+13307G>A	intron	N/A	ENSP00000441362.1	F5GYZ5
SOD2	ENST00000535561.5	TSL:3	c.92+12893G>A	intron	N/A	ENSP00000445015.1	F5H4R2
SOD2	ENST00000546087.5	TSL:2	c.-116+16926G>A	intron	N/A	ENSP00000442920.1	P04179-4

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61277

AN:

151674

Hom.:

13684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.390

AC:

248900

AN:

638396

Hom.:

53627

Cov.:

AF XY:

0.396

AC XY:

132096

AN XY:

333888

show subpopulations

African (AFR)

AF:

0.164

AC:

2913

AN:

17794

American (AMR)

AF:

0.573

AC:

13196

AN:

23026

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

6176

AN:

13938

East Asian (EAS)

AF:

0.155

AC:

5004

AN:

32290

South Asian (SAS)

AF:

0.441

AC:

22369

AN:

50716

European-Finnish (FIN)

AF:

0.467

AC:

21596

AN:

46222

Middle Eastern (MID)

AF:

0.395

AC:

1509

AN:

3820

European-Non Finnish (NFE)

AF:

0.391

AC:

163885

AN:

419564

Other (OTH)

AF:

0.395

AC:

12252

AN:

31026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

5689

11377

17066

22754

28443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2330

4660

6990

9320

11650

<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:

0.404

AC:

61279

AN:

151792

Hom.:

13691

Cov.:

AF XY:

0.402

AC XY:

29847

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.214

AC:

8880

AN:

41402

American (AMR)

AF:

0.520

AC:

7928

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1714

AN:

3466

East Asian (EAS)

AF:

0.180

AC:

926

AN:

5156

South Asian (SAS)

AF:

0.470

AC:

2249

AN:

4782

European-Finnish (FIN)

AF:

0.462

AC:

4863

AN:

10526

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33255

AN:

67902

Other (OTH)

AF:

0.417

AC:

880

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1757

3514

5270

7027

8784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.444

Hom.:

2072

Bravo

AF:

0.397

Asia WGS

AF:

0.332

AC:

1154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.3

(source)

DANN

Benign

0.70

PhyloP100

0.062

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over