4-24796559-C-T

Variant names:

• chr4-24796559-C-T
• rs2695231
• NM_003102.4:c.-17+908C>T

Variant summary

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

The NM_003102.4(SOD3):​c.-17+908C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 147,302 control chromosomes in the GnomAD database, including 22,821 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 0.51 (22821 hom., cov: 23)
• Consequence: SOD3 NM_003102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811
• Publications: 0 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4	c.-17+908C>T		intron_variant	Intron 1 of 1	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.79+908C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.-17+908C>T		intron_variant	Intron 1 of 1	1	NM_003102.4	ENSP00000371554.3
SOD3	ENST00000598411.1	c.-16-2947C>T		intron_variant	Intron 2 of 2	5		ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 75248 AN: 147220 Hom.: 22827 Cov.: 23

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.511 AC: 75235 AN: 147302 Hom.: 22821 Cov.: 23 AF XY: 0.514 AC XY: 36828 AN XY: 71608

African (AFR) AF: 0.174 AC: 6880 AN: 39604

American (AMR) AF: 0.542 AC: 8007 AN: 14764

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1974 AN: 3444

East Asian (EAS) AF: 0.369 AC: 1806 AN: 4896

South Asian (SAS) AF: 0.515 AC: 2359 AN: 4580

European-Finnish (FIN) AF: 0.778 AC: 7472 AN: 9608

Middle Eastern (MID) AF: 0.431 AC: 118 AN: 274

European-Non Finnish (NFE) AF: 0.668 AC: 44900 AN: 67202

Other (OTH) AF: 0.529 AC: 1071 AN: 2026

Alfa AF: 0.466 Hom.: 1627

Bravo AF: 0.474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2695231; hg19: chr4-24798181;