rs4523113

Variant names:

• chr6-159685203-T-A
• rs4523113
• NM_000636.4:c.344-170A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-159685203-T-A
• chr6-159685203-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000636.4(SOD2):​c.344-170A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 147,620 control chromosomes in the GnomAD database, including 3,603 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 0.21 (3603 hom., cov: 28)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.344-170A>T		intron_variant	Intron 3 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.344-170A>T		intron_variant	Intron 3 of 4	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 31570 AN: 147520 Hom.: 3600 Cov.: 28

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0309

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.214 AC: 31579 AN: 147620 Hom.: 3603 Cov.: 28 AF XY: 0.219 AC XY: 15668 AN XY: 71610

African (AFR) AF: 0.143 AC: 5782 AN: 40422

American (AMR) AF: 0.223 AC: 3233 AN: 14508

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 686 AN: 3444

East Asian (EAS) AF: 0.392 AC: 1973 AN: 5030

South Asian (SAS) AF: 0.267 AC: 1260 AN: 4716

European-Finnish (FIN) AF: 0.292 AC: 2621 AN: 8962

Middle Eastern (MID) AF: 0.196 AC: 56 AN: 286

European-Non Finnish (NFE) AF: 0.230 AC: 15479 AN: 67288

Other (OTH) AF: 0.224 AC: 461 AN: 2058

Alfa AF: 0.220 Hom.: 404

Bravo AF: 0.212

Asia WGS AF: 0.302 AC: 1047 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.19
PhyloP100		1.0
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: rs4523113; hg19: chr6-160106235;