rs8192287

Positions:

• chr4-24794946-G-T

Variant summary

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

The ENST00000598411.1(SOD3):​c.-16-4560G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,156 control chromosomes in the GnomAD database, including 307 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 0.051 (307 hom., cov: 31)
• Consequence: SOD3 ENST00000598411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000598411.1	c.-16-4560G>T		intron_variant		5		ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7716 AN: 152038 Hom.: 307 Cov.: 31

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0503

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

GnomAD4 genome AF: 0.0508 AC: 7723 AN: 152156 Hom.: 307 Cov.: 31 AF XY: 0.0505 AC XY: 3756 AN XY: 74390

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.0693

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.0928

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0615

Gnomad4 OTH AF: 0.0503

Alfa AF: 0.0589 Hom.: 276

Bravo AF: 0.0509

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192287; hg19: chr4-24796568;