rs927450

Positions:

• chr6-159761064-A-G

Variant summary

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

The NR_037166.1(SOD2-OT1):​n.912T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 153,446 control chromosomes in the GnomAD database, including 18,128 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 0.46 (17953 hom., cov: 32)
  • Exomes 𝑓: 0.43 (175 hom.)
• Consequence: SOD2-OT1 NR_037166.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

Genes affected

SOD2-OT1 (HGNC:53445): (SOD2 overlapping transcript 1)

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2-OT1	NR_037166.1	n.912T>C		non_coding_transcript_exon_variant	2/2
SOD2	NM_001322817.2	c.-363T>C		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2-OT1	ENST00000535372.1	n.912T>C		non_coding_transcript_exon_variant	2/2	1
SOD2	ENST00000546087.5	c.-363T>C		5_prime_UTR_variant	1/8	2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69283 AN: 151944 Hom.: 17947 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.434 AC: 601 AN: 1384 Hom.: 175 Cov.: 0 AF XY: 0.441 AC XY: 377 AN XY: 854

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.456 AC: 69282 AN: 152062 Hom.: 17953 Cov.: 32 AF XY: 0.454 AC XY: 33755 AN XY: 74322

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.456

Alfa AF: 0.557 Hom.: 26592

Bravo AF: 0.443

Asia WGS AF: 0.349 AC: 1214 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	3.9
DANN	Benign	0.82

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: rs927450; hg19: chr6-160182096;