NM_000636.4:c.523+1042C>A

Variant names:

• chr6-159683812-G-T
• rs2758330
• NM_000636.4:c.523+1042C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

SOD2 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.523+1042C>A		intron_variant	Intron 4 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.523+1042C>A		intron_variant	Intron 4 of 4	1	NM_000636.4	ENSP00000446252.1

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

African (AFR) AF: 0.700 AC: 28989 AN: 41428

American (AMR) AF: 0.830 AC: 12670 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2631 AN: 3472

East Asian (EAS) AF: 0.536 AC: 2756 AN: 5138

South Asian (SAS) AF: 0.852 AC: 4113 AN: 4826

European-Finnish (FIN) AF: 0.836 AC: 8827 AN: 10558

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54104 AN: 67976

Other (OTH) AF: 0.773 AC: 1632 AN: 2112

Alfa AF: 0.775 Hom.: 15480

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
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2758330; hg19: chr6-160104844;