rs5746105

Positions:

• chr6-159691606-A-G
• chr6-159691606-A-T

Variant summary

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

The ENST00000452684.2(SOD2):​c.*858T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,028 control chromosomes in the GnomAD database, including 6,251 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 0.29 (6251 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOD2 ENST00000452684.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_000636.4	c.226+1055T>C		intron_variant		ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.226+1055T>C		intron_variant		1	NM_000636.4	ENSP00000446252	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43393 AN: 151910 Hom.: 6244 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.295

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.286 AC: 43423 AN: 152028 Hom.: 6251 Cov.: 32 AF XY: 0.292 AC XY: 21717 AN XY: 74300

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.293

Alfa AF: 0.289 Hom.: 2977

Bravo AF: 0.277

Asia WGS AF: 0.334 AC: 1160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.27

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: rs5746105; hg19: chr6-160112638;