6-159693334-C-T

Position:

• chr6-159693334-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001322817.2(SOD2):​c.-115-471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 296,408 control chromosomes in the GnomAD database, including 16,469 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 0.30 (5311 hom., cov: 23)
  • Exomes 𝑓: 0.35 (11158 hom.)
• Consequence: SOD2 NM_001322817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_001322817.2	c.-115-471G>A		intron_variant			NP_001309746.1
SOD2	NM_001322819.2	c.-115-471G>A		intron_variant			NP_001309748.1
SOD2	NM_001322820.2	c.-115-471G>A		intron_variant			NP_001309749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000545162.5	c.93-471G>A		intron_variant		3		ENSP00000441362.1
SOD2	ENST00000535561.5	c.93-471G>A		intron_variant		3		ENSP00000445015.1
SOD2	ENST00000546087.5	c.-115-471G>A		intron_variant		2		ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 40467 AN: 136792 Hom.: 5302 Cov.: 23

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.305

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.345 AC: 55085 AN: 159540 Hom.: 11158 Cov.: 4 AF XY: 0.346 AC XY: 28602 AN XY: 82638

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.296 AC: 40491 AN: 136868 Hom.: 5311 Cov.: 23 AF XY: 0.301 AC XY: 19989 AN XY: 66362

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.297

Alfa AF: 0.100 Hom.: 88

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.1
DANN	Benign	0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5746091; hg19: chr6-160114366; COSMIC: COSV61622775; COSMIC: COSV61622775;