rs2239585

chr4-24792697-G-Achr4-24792697-G-C

Variant summary

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

The ENST00000598411.1(SOD3):c.-17+2595G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,998 control chromosomes in the GnomAD database, including 2,194 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 0.15 (2194 hom., cov: 32)
• Consequence: SOD3 ENST00000598411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

Genes affected

SOD3 (HGNC:11181): (superoxide dismutase 3) This gene encodes a member of the superoxide dismutase (SOD) protein family. SODs are antioxidant enzymes that catalyze the conversion of superoxide radicals into hydrogen peroxide and oxygen, which may protect the brain, lungs, and other tissues from oxidative stress. Proteolytic processing of the encoded protein results in the formation of two distinct homotetramers that differ in their ability to interact with the extracellular matrix (ECM). Homotetramers consisting of the intact protein, or type C subunit, exhibit high affinity for heparin and are anchored to the ECM. Homotetramers consisting of a proteolytically cleaved form of the protein, or type A subunit, exhibit low affinity for heparin and do not interact with the ECM. A mutation in this gene may be associated with increased heart disease risk. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD3	ENST00000598411.1	c.-17+2595G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23441 AN: 151882 Hom.: 2188 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0918

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.154 AC: 23478 AN: 151998 Hom.: 2194 Cov.: 32 AF XY: 0.158 AC XY: 11709 AN XY: 74284

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.140

Alfa AF: 0.0111 Hom.: 6

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.2
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239585; hg19: chr4-24794319;