Genetic Variant ENST00000452684.2:c.*175G>A (chr6-159692289-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 ENST00000452684.2(SOD2):c.*175G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 724,018 control chromosomes in the GnomAD database, including 85,733 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 0.47 ( 17298 hom., cov: 31)

Exomes 𝑓: 0.48 ( 68435 hom. )

Consequence

SOD2
ENST00000452684.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

Publications

14 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:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.226+372G>A		intron_variant	Intron 2 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.226+372G>A		intron_variant	Intron 2 of 4	1	NM_000636.4	ENSP00000446252.1		P04179-1

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71530

AN:

151914

Hom.:

17282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.480

AC:

274674

AN:

571984

Hom.:

68435

Cov.:

AF XY:

0.481

AC XY:

134842

AN XY:

280566

show subpopulations

African (AFR)

AF:

0.427

AC:

5621

AN:

13166

American (AMR)

AF:

0.574

AC:

4648

AN:

8104

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

5747

AN:

11422

East Asian (EAS)

AF:

0.128

AC:

3129

AN:

24386

South Asian (SAS)

AF:

0.524

AC:

6663

AN:

12706

European-Finnish (FIN)

AF:

0.481

AC:

12541

AN:

26074

Middle Eastern (MID)

AF:

0.445

AC:

1007

AN:

2264

European-Non Finnish (NFE)

AF:

0.498

AC:

222575

AN:

446718

Other (OTH)

AF:

0.469

AC:

12743

AN:

27144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6759

13518

20278

27037

33796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.471

AC:

71575

AN:

152034

Hom.:

17298

Cov.:

AF XY:

0.466

AC XY:

34609

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.426

AC:

17662

AN:

41464

American (AMR)

AF:

0.537

AC:

8205

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1796

AN:

3462

East Asian (EAS)

AF:

0.143

AC:

739

AN:

5174

South Asian (SAS)

AF:

0.513

AC:

2471

AN:

4816

European-Finnish (FIN)

AF:

0.466

AC:

4918

AN:

10560

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34203

AN:

67964

Other (OTH)

AF:

0.473

AC:

998

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1909

3819

5728

7638

9547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.496

Hom.:

9158

Bravo

AF:

0.472

Asia WGS

AF:

0.350

AC:

1218

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

(source)

DANN

Benign

0.59

PhyloP100

-0.017

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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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ENST00000452684.2:c.*175G>A

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