rs2758330

Positions:

• chr6-159683812-G-T

Variant summary

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

The NM_000636.4(SOD2):​c.523+1042C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 151,978 control chromosomes in the GnomAD database, including 45,131 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 0.77 (45131 hom., cov: 31)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_000636.4	c.523+1042C>A		intron_variant		ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.523+1042C>A		intron_variant		1	NM_000636.4	ENSP00000446252	P1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116454 AN: 151860 Hom.: 45102 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.778

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.767 AC: 116529 AN: 151978 Hom.: 45131 Cov.: 31 AF XY: 0.768 AC XY: 57044 AN XY: 74244

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.773

Alfa AF: 0.790 Hom.: 7941

Bravo AF: 0.760

Asia WGS AF: 0.687 AC: 2388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.74

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: rs2758330; hg19: chr6-160104844;