Genetic Variant ENST00000545162.5:c.93-471G>A (chr6-159693334-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000545162.5(SOD2):c.93-471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 296,408 control chromosomes in the GnomAD database, including 16,469 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 0.30 ( 5311 hom., cov: 23)

Exomes 𝑓: 0.35 ( 11158 hom. )

Consequence

SOD2
ENST00000545162.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0830

Publications

4 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4 link	c.-167G>A		upstream_gene_variant		ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7 link	c.-167G>A		upstream_gene_variant		1	NM_000636.4	ENSP00000446252.1		P04179-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

40467

AN:

136792

Hom.:

5302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.305

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.298

GnomAD4 exome

AF:

0.345

AC:

55085

AN:

159540

Hom.:

11158

Cov.:

AF XY:

0.346

AC XY:

28602

AN XY:

82638

show subpopulations

African (AFR)

AF:

0.363

AC:

1206

AN:

3320

American (AMR)

AF:

0.355

AC:

1139

AN:

3204

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

1302

AN:

3652

East Asian (EAS)

AF:

0.495

AC:

4829

AN:

9762

South Asian (SAS)

AF:

0.334

AC:

992

AN:

2966

European-Finnish (FIN)

AF:

0.433

AC:

4962

AN:

11456

Middle Eastern (MID)

AF:

0.470

AC:

324

AN:

690

European-Non Finnish (NFE)

AF:

0.321

AC:

37331

AN:

116406

Other (OTH)

AF:

0.371

AC:

3000

AN:

8084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.636

Heterozygous variant carriers

1087

2173

3260

4346

5433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.296

AC:

40491

AN:

136868

Hom.:

5311

Cov.:

AF XY:

0.301

AC XY:

19989

AN XY:

66362

show subpopulations

African (AFR)

AF:

0.311

AC:

11394

AN:

36638

American (AMR)

AF:

0.292

AC:

4147

AN:

14182

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

862

AN:

3306

East Asian (EAS)

AF:

0.377

AC:

1717

AN:

4550

South Asian (SAS)

AF:

0.315

AC:

1400

AN:

4438

European-Finnish (FIN)

AF:

0.347

AC:

2788

AN:

8046

Middle Eastern (MID)

AF:

0.314

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.278

AC:

17427

AN:

62734

Other (OTH)

AF:

0.297

AC:

564

AN:

1896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.591

Heterozygous variant carriers

1171

2342

3514

4685

5856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.100

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.1

(source)

DANN

Benign

0.95

PhyloP100

-0.083

PromoterAI

-0.073

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over