chr4-24797878-T-A

Variant names:

• chr4-24797878-T-A
• rs17881426
• NM_003102.4:c.-16-1628T>A

Variant summary

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

The NM_003102.4(SOD3):​c.-16-1628T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,162 control chromosomes in the GnomAD database, including 2,238 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 (2238 hom., cov: 32)
• Consequence: SOD3 NM_003102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4	c.-16-1628T>A		intron_variant	Intron 1 of 1	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.80-1628T>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.-16-1628T>A		intron_variant	Intron 1 of 1	1	NM_003102.4	ENSP00000371554.3
SOD3	ENST00000598411.1	c.-16-1628T>A		intron_variant	Intron 2 of 2	5		ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22905 AN: 152044 Hom.: 2230 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.151 AC: 22950 AN: 152162 Hom.: 2238 Cov.: 32 AF XY: 0.152 AC XY: 11321 AN XY: 74392

African (AFR) AF: 0.254 AC: 10527 AN: 41496

American (AMR) AF: 0.204 AC: 3122 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3472

East Asian (EAS) AF: 0.127 AC: 658 AN: 5162

South Asian (SAS) AF: 0.212 AC: 1023 AN: 4818

European-Finnish (FIN) AF: 0.0597 AC: 633 AN: 10604

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6094 AN: 68012

Other (OTH) AF: 0.138 AC: 291 AN: 2108

Alfa AF: 0.0293 Hom.: 25

Bravo AF: 0.165

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.76
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17881426; hg19: chr4-24799500;