ENST00000598411.1:c.-17+3073T>G

Variant names:

• chr4-24793175-T-G
• rs2284659
• ENST00000598411.1:c.-17+3073T>G

Variant summary

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

The ENST00000598411.1(SOD3):​c.-17+3073T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,046 control chromosomes in the GnomAD database, including 22,381 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 0.50 (22381 hom., cov: 32)
• Consequence: SOD3 ENST00000598411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 24 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000598411.1	c.-17+3073T>G		intron_variant	Intron 2 of 2	5		ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75456 AN: 151928 Hom.: 22384 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.496 AC: 75460 AN: 152046 Hom.: 22381 Cov.: 32 AF XY: 0.498 AC XY: 37050 AN XY: 74324

African (AFR) AF: 0.169 AC: 6995 AN: 41494

American (AMR) AF: 0.531 AC: 8115 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3468

East Asian (EAS) AF: 0.356 AC: 1834 AN: 5156

South Asian (SAS) AF: 0.500 AC: 2407 AN: 4810

European-Finnish (FIN) AF: 0.712 AC: 7524 AN: 10564

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44823 AN: 67978

Other (OTH) AF: 0.513 AC: 1078 AN: 2100

Alfa AF: 0.603 Hom.: 49230

Bravo AF: 0.468

Asia WGS AF: 0.428 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.47
PhyloP100		0.0070

Splicing

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

Other links and lift over

dbSNP: rs2284659; hg19: chr4-24794797;