rs5746094

Positions:

• chr6-159693136-T-C

Variant summary

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

The NM_000636.4(SOD2):​c.23+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,529,256 control chromosomes in the GnomAD database, including 45,599 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 0.23 (4232 hom., cov: 31)
  • Exomes 𝑓: 0.24 (41367 hom.)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD2	NM_000636.4	c.23+9A>G		intron_variant		ENST00000538183.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD2	ENST00000538183.7	c.23+9A>G		intron_variant		1	NM_000636.4	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35168 AN: 151666 Hom.: 4230 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.238

GnomAD3 exomes AF: 0.247 AC: 32795 AN: 132636 Hom.: 4385 AF XY: 0.248 AC XY: 17665 AN XY: 71134

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.381

Gnomad SAS exome AF: 0.257

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.240

GnomAD4 exome AF: 0.242 AC: 333911 AN: 1377482 Hom.: 41367 Cov.: 33 AF XY: 0.244 AC XY: 165871 AN XY: 679418

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.232 AC: 35182 AN: 151774 Hom.: 4232 Cov.: 31 AF XY: 0.239 AC XY: 17694 AN XY: 74164

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.237

Alfa AF: 0.231 Hom.: 2571

Bravo AF: 0.223

Asia WGS AF: 0.301 AC: 1039 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.8
DANN	Benign	0.43

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: rs5746094; hg19: chr6-160114168; COSMIC: COSV61623032; COSMIC: COSV61623032;