rs6917589

Positions:

• chr6-159678228-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538183.7(SOD2):​c.*4265A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,090 control chromosomes in the GnomAD database, including 4,012 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 0.22 (4008 hom., cov: 32)
  • Exomes 𝑓: 0.26 (4 hom.)
• Consequence: SOD2 ENST00000538183.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_000636.4	c.*4265A>G		3_prime_UTR_variant	5/5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.*4265A>G		3_prime_UTR_variant	5/5	1	NM_000636.4	ENSP00000446252	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33816 AN: 151892 Hom.: 4004 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.263 AC: 21 AN: 80 Hom.: 4 Cov.: 0 AF XY: 0.288 AC XY: 19 AN XY: 66

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.223 AC: 33834 AN: 152010 Hom.: 4008 Cov.: 32 AF XY: 0.230 AC XY: 17068 AN XY: 74270

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.229

Alfa AF: 0.233 Hom.: 4718

Bravo AF: 0.214

Asia WGS AF: 0.304 AC: 1056 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	4.7
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs6917589; hg19: chr6-160099260;