4-24793891-C-T

Position:

• chr4-24793891-C-T

Variant summary

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

The ENST00000598411.1(SOD3):​c.-17+3789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,648 control chromosomes in the GnomAD database, including 2,016 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 (2016 hom., cov: 31)
• Consequence: SOD3 ENST00000598411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 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.-17+3789C>T		intron_variant		5		ENSP00000472134

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22550 AN: 151530 Hom.: 2010 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.149 AC: 22587 AN: 151648 Hom.: 2016 Cov.: 31 AF XY: 0.152 AC XY: 11264 AN XY: 74072

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0917

Gnomad4 OTH AF: 0.138

Alfa AF: 0.131 Hom.: 149

Bravo AF: 0.158

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.1
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13306703; hg19: chr4-24795513;