rs699473

Variant names:

• chr4-24795181-C-T
• rs699473
• ENST00000598411.1:c.-16-4325C>T

Variant summary

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

The ENST00000598411.1(SOD3):​c.-16-4325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,956 control chromosomes in the GnomAD database, including 24,351 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 0.54 (24351 hom., cov: 31)
• Consequence: SOD3 ENST00000598411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 47 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 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.-16-4325C>T		intron_variant	Intron 2 of 2	5		ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82084 AN: 151838 Hom.: 24351 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.540 AC: 82097 AN: 151956 Hom.: 24351 Cov.: 31 AF XY: 0.541 AC XY: 40211 AN XY: 74272

African (AFR) AF: 0.306 AC: 12658 AN: 41420

American (AMR) AF: 0.552 AC: 8428 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3470

East Asian (EAS) AF: 0.346 AC: 1776 AN: 5132

South Asian (SAS) AF: 0.502 AC: 2412 AN: 4800

European-Finnish (FIN) AF: 0.726 AC: 7662 AN: 10558

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.667 AC: 45318 AN: 67980

Other (OTH) AF: 0.540 AC: 1143 AN: 2116

Alfa AF: 0.617 Hom.: 113206

Bravo AF: 0.516

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.031
DANN	Benign	0.60
PhyloP100		-1.8
PromoterAI		-0.054	Neutral

Splicing

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

Other links and lift over

dbSNP: rs699473; hg19: chr4-24796803;