dbSNP rs927450: SOD2-OT1:n.912T>C (chr6-159761064-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000535372.1(SOD2-OT1):n.912T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 153,446 control chromosomes in the GnomAD database, including 18,128 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 0.46 ( 17953 hom., cov: 32)

Exomes 𝑓: 0.43 ( 175 hom. )

Consequence

SOD2-OT1
ENST00000535372.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.150

Publications

22 publications found

Variant links:

Genes affected

SOD2-OT1 (HGNC:53445): (SOD2 overlapping transcript 1)

SOD2-OT1 links:

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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2-OT1	NR_037166.1 link	n.912T>C		non_coding_transcript_exon_variant	Exon 2 of 2
SOD2	NM_001322817.2 link	c.-363T>C		5_prime_UTR_variant	Exon 1 of 8		NP_001309746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2-OT1	ENST00000535372.1 link	n.912T>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
SOD2	ENST00000546087.5 link	c.-363T>C		5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000442920.1

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69283

AN:

151944

Hom.:

17947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.461

GnomAD4 exome

AF:

0.434

AC:

601

AN:

1384

Hom.:

175

Cov.:

AF XY:

0.441

AC XY:

377

AN XY:

854

show subpopulations

African (AFR)

AF:

0.227

AC:

AN:

American (AMR)

AF:

0.550

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

AN:

East Asian (EAS)

AF:

0.0500

AC:

AN:

South Asian (SAS)

AF:

0.412

AC:

197

AN:

478

European-Finnish (FIN)

AF:

0.444

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

316

AN:

702

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.456

AC:

69282

AN:

152062

Hom.:

17953

Cov.:

AF XY:

0.454

AC XY:

33755

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.219

AC:

9082

AN:

41480

American (AMR)

AF:

0.543

AC:

8301

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1957

AN:

3472

East Asian (EAS)

AF:

0.178

AC:

920

AN:

5166

South Asian (SAS)

AF:

0.495

AC:

2383

AN:

4816

European-Finnish (FIN)

AF:

0.562

AC:

5930

AN:

10554

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.576

AC:

39152

AN:

67984

Other (OTH)

AF:

0.456

AC:

964

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1731

3462

5192

6923

8654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.538

Hom.:

36224

Bravo

AF:

0.443

Asia WGS

AF:

0.349

AC:

1214

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.9

(source)

DANN

Benign

0.82

PhyloP100

-0.15

Mutation Taster

=294/6

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