rs8031

Variant names:

• chr6-159679608-A-T
• rs8031
• NM_000636.4:c.*2885T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000636.4(SOD2):​c.*2885T>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 0.431 in 152,072 control chromosomes in the GnomAD database, including 14,860 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 0.43 (14860 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 38 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.*2885T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.*2885T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65577 AN: 151954 Hom.: 14848 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.441

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.431 AC: 65590 AN: 152072 Hom.: 14860 Cov.: 32 AF XY: 0.428 AC XY: 31801 AN XY: 74314

African (AFR) AF: 0.324 AC: 13448 AN: 41500

American (AMR) AF: 0.497 AC: 7594 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3472

East Asian (EAS) AF: 0.132 AC: 686 AN: 5186

South Asian (SAS) AF: 0.477 AC: 2300 AN: 4818

European-Finnish (FIN) AF: 0.462 AC: 4877 AN: 10546

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33538 AN: 67960

Other (OTH) AF: 0.437 AC: 924 AN: 2116

Alfa AF: 0.475 Hom.: 2299

Bravo AF: 0.427

Asia WGS AF: 0.323 AC: 1122 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	4.5
DANN	Benign	0.54
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8031; hg19: chr6-160100640;