4-24795056-G-T

Variant names:

• chr4-24795056-G-T
• rs8192288
• ENST00000598411.1:c.-16-4450G>T

Variant summary

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

The ENST00000598411.1(SOD3):​c.-16-4450G>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 152,050 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: -0.113
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598411.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD3	ENST00000598411.1	TSL:5	c.-16-4450G>T		intron	N/A	ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7720 AN: 151932 Hom.: 307 Cov.: 31

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0935

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0508 AC: 7727 AN: 152050 Hom.: 307 Cov.: 31 AF XY: 0.0505 AC XY: 3755 AN XY: 74288

African (AFR) AF: 0.0124 AC: 515 AN: 41496

American (AMR) AF: 0.0695 AC: 1062 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3472

East Asian (EAS) AF: 0.0935 AC: 479 AN: 5124

South Asian (SAS) AF: 0.171 AC: 819 AN: 4796

European-Finnish (FIN) AF: 0.0237 AC: 251 AN: 10598

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0614 AC: 4174 AN: 67966

Other (OTH) AF: 0.0517 AC: 109 AN: 2110

Alfa AF: 0.0212 Hom.: 12

Bravo AF: 0.0510

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.61
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs8192288; hg19: chr4-24796678;