4-24796575-A-G

Variant names:

• chr4-24796575-A-G
• rs2536511
• NM_003102.4:c.-17+924A>G

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+924A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 145,520 control chromosomes in the GnomAD database, including 22,923 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 0.52 (22923 hom., cov: 24)
• Consequence: SOD3 NM_003102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4	c.-17+924A>G		intron_variant	Intron 1 of 1	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.79+924A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.-17+924A>G		intron_variant	Intron 1 of 1	1	NM_003102.4	ENSP00000371554.3
SOD3	ENST00000598411.1	c.-16-2931A>G		intron_variant	Intron 2 of 2	5		ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 75474 AN: 145454 Hom.: 22929 Cov.: 24

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.519 AC: 75461 AN: 145520 Hom.: 22923 Cov.: 24 AF XY: 0.522 AC XY: 36940 AN XY: 70760

African (AFR) AF: 0.181 AC: 6900 AN: 38072

American (AMR) AF: 0.546 AC: 8015 AN: 14690

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1982 AN: 3436

East Asian (EAS) AF: 0.372 AC: 1823 AN: 4894

South Asian (SAS) AF: 0.519 AC: 2366 AN: 4558

European-Finnish (FIN) AF: 0.786 AC: 7558 AN: 9616

Middle Eastern (MID) AF: 0.440 AC: 118 AN: 268

European-Non Finnish (NFE) AF: 0.670 AC: 44976 AN: 67086

Other (OTH) AF: 0.535 AC: 1072 AN: 2002

Alfa AF: 0.573 Hom.: 2986

Bravo AF: 0.474

Asia WGS AF: 0.429 AC: 1484 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.48
PhyloP100		-0.55
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: rs2536511; hg19: chr4-24798197;