rs5746112

Variant names:

• chr6-159688512-GGAAAT-G
• rs5746112
• NM_000636.4:c.227-275_227-271delATTTC

Your query was ambiguous. Multiple possible variants found:

• chr6-159688512-GGAAAT-G
• chr6-159688512-GGAAAT-GGAAATGAAAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000636.4(SOD2):​c.227-275_227-271delATTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14560 hom., cov: 0)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.227-275_227-271delATTTC		intron_variant	Intron 2 of 4	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.227-275_227-271delATTTC		intron_variant	Intron 2 of 4	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64918 AN: 151272 Hom.: 14547 Cov.: 0

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.429 AC: 64934 AN: 151392 Hom.: 14560 Cov.: 0 AF XY: 0.425 AC XY: 31433 AN XY: 73936

African (AFR) AF: 0.320 AC: 13197 AN: 41302

American (AMR) AF: 0.495 AC: 7526 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1648 AN: 3460

East Asian (EAS) AF: 0.132 AC: 684 AN: 5174

South Asian (SAS) AF: 0.475 AC: 2285 AN: 4806

European-Finnish (FIN) AF: 0.460 AC: 4813 AN: 10452

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.492 AC: 33312 AN: 67712

Other (OTH) AF: 0.436 AC: 914 AN: 2098

Alfa AF: 0.474 Hom.: 2106

Bravo AF: 0.426

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5746112; hg19: chr6-160109544;