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GeneBe

rs4880

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000636.4(SOD2):c.47T>C(p.Val16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,610,644 control chromosomes in the GnomAD database, including 197,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,risk factor (no stars).

Frequency

Genomes: 𝑓 0.47 ( 17262 hom., cov: 32)
Exomes 𝑓: 0.49 ( 180259 hom. )

Consequence

SOD2
NM_000636.4 missense

Scores

1
14

Clinical Significance

Conflicting classifications of pathogenicity; risk factor no assertion criteria provided P:1B:1O:1

Conservation

PhyloP100: 2.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=3.9671322E-5).
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/exons MANE UniProt
SOD2NM_000636.4 linkuse as main transcriptc.47T>C p.Val16Ala missense_variant 2/5 ENST00000538183.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOD2ENST00000538183.7 linkuse as main transcriptc.47T>C p.Val16Ala missense_variant 2/51 NM_000636.4 P1P04179-1

Frequencies

GnomAD3 genomes
AF:
0.470
AC:
71427
AN:
151824
Hom.:
17245
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.425
Gnomad AMI
AF:
0.490
Gnomad AMR
AF:
0.536
Gnomad ASJ
AF:
0.519
Gnomad EAS
AF:
0.144
Gnomad SAS
AF:
0.513
Gnomad FIN
AF:
0.467
Gnomad MID
AF:
0.481
Gnomad NFE
AF:
0.503
Gnomad OTH
AF:
0.474
GnomAD3 exomes
AF:
0.484
AC:
117709
AN:
243226
Hom.:
29854
AF XY:
0.484
AC XY:
63735
AN XY:
131784
show subpopulations
Gnomad AFR exome
AF:
0.425
Gnomad AMR exome
AF:
0.623
Gnomad ASJ exome
AF:
0.513
Gnomad EAS exome
AF:
0.137
Gnomad SAS exome
AF:
0.519
Gnomad FIN exome
AF:
0.472
Gnomad NFE exome
AF:
0.497
Gnomad OTH exome
AF:
0.485
GnomAD4 exome
AF:
0.492
AC:
717843
AN:
1458702
Hom.:
180259
Cov.:
48
AF XY:
0.491
AC XY:
356365
AN XY:
725526
show subpopulations
Gnomad4 AFR exome
AF:
0.429
Gnomad4 AMR exome
AF:
0.613
Gnomad4 ASJ exome
AF:
0.506
Gnomad4 EAS exome
AF:
0.131
Gnomad4 SAS exome
AF:
0.519
Gnomad4 FIN exome
AF:
0.481
Gnomad4 NFE exome
AF:
0.501
Gnomad4 OTH exome
AF:
0.476
GnomAD4 genome
AF:
0.470
AC:
71475
AN:
151942
Hom.:
17262
Cov.:
32
AF XY:
0.466
AC XY:
34579
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.425
Gnomad4 AMR
AF:
0.537
Gnomad4 ASJ
AF:
0.519
Gnomad4 EAS
AF:
0.144
Gnomad4 SAS
AF:
0.512
Gnomad4 FIN
AF:
0.467
Gnomad4 NFE
AF:
0.503
Gnomad4 OTH
AF:
0.469
Alfa
AF:
0.488
Hom.:
30554
Bravo
AF:
0.472
TwinsUK
AF:
0.490
AC:
1818
ALSPAC
AF:
0.477
AC:
1839
ESP6500AA
AF:
0.420
AC:
1849
ESP6500EA
AF:
0.500
AC:
4303
ExAC
AF:
0.476
AC:
57687
Asia WGS
AF:
0.349
AC:
1214
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity; risk factor
Submissions summary: Pathogenic:1Benign:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Microvascular complications of diabetes, susceptibility to, 6 Pathogenic:1Other:1
Likely risk allele, no assertion criteria providedreference populationiDNA GenomicsJan 01, 2007- -
risk factor, no assertion criteria providedliterature onlyOMIMJan 01, 2007- -
SUPEROXIDE DISMUTASE 2 POLYMORPHISM Benign:1
Benign, no assertion criteria providedliterature onlyOMIMJan 01, 2007- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.61
Cadd
Benign
8.2
Dann
Benign
0.82
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.13
N
MetaRNN
Benign
0.000040
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
P;P;P;P;P;P;P
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
0.35
N;N;N;N;N;N;N;N
REVEL
Benign
0.048
Sift
Benign
0.93
T;T;T;T;T;T;T;T
Sift4G
Benign
0.98
T;T;T;T;T;.;.;T
Polyphen
0.024
.;.;.;.;.;.;.;B
Vest4
0.034
MPC
0.56
ClinPred
0.0093
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.020
gMVP
0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4880; hg19: chr6-160113872; COSMIC: COSV61622991; COSMIC: COSV61622991; API