4-24796559-C-T

Position:

• chr4-24796559-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

SOD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SOD3	NM_003102.4	c.-17+908C>T		intron_variant		ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.79+908C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.-17+908C>T		intron_variant		1	NM_003102.4	ENSP00000371554.3
SOD3	ENST00000598411.1	c.-16-2947C>T		intron_variant		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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.529

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2695231; hg19: chr4-24798181;