rs2070994

Positions:

• chr6-159688019-A-T

Variant summary

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

The NM_000636.4(SOD2):​c.343+107T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 723,186 control chromosomes in the GnomAD database, including 76,882 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 0.40 (13610 hom., cov: 31)
  • Exomes 𝑓: 0.46 (63272 hom.)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.343+107T>A		intron_variant		ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.343+107T>A		intron_variant		1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61143 AN: 151766 Hom.: 13600 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.458 AC: 261759 AN: 571300 Hom.: 63272 AF XY: 0.459 AC XY: 141199 AN XY: 307292

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.403 AC: 61151 AN: 151886 Hom.: 13610 Cov.: 31 AF XY: 0.400 AC XY: 29707 AN XY: 74232

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.416

Alfa AF: 0.456 Hom.: 2063

Bravo AF: 0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.55

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: rs2070994; hg19: chr6-160109051; COSMIC: COSV61622898; COSMIC: COSV61622898;