chr4-24800354-T-C

Variant names:

• chr4-24800354-T-C
• rs2855262
• NM_003102.4:c.*110T>C

Variant summary

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

The NM_003102.4(SOD3):​c.*110T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,150,044 control chromosomes in the GnomAD database, including 222,949 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 0.50 (22328 hom., cov: 30)
  • Exomes 𝑓: 0.63 (200621 hom.)
• Consequence: SOD3 NM_003102.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 25 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4	c.*110T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.928T>C		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.*110T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_003102.4	ENSP00000371554.3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75769 AN: 151636 Hom.: 22331 Cov.: 30

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.627 AC: 626093 AN: 998290 Hom.: 200621 Cov.: 14 AF XY: 0.627 AC XY: 301452 AN XY: 480780

African (AFR) AF: 0.152 AC: 3012 AN: 19810

American (AMR) AF: 0.515 AC: 4063 AN: 7884

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 8522 AN: 13774

East Asian (EAS) AF: 0.340 AC: 8419 AN: 24768

South Asian (SAS) AF: 0.528 AC: 16254 AN: 30798

European-Finnish (FIN) AF: 0.686 AC: 27312 AN: 39810

Middle Eastern (MID) AF: 0.556 AC: 1524 AN: 2742

European-Non Finnish (NFE) AF: 0.651 AC: 532475 AN: 817602

Other (OTH) AF: 0.596 AC: 24512 AN: 41102

GnomAD4 genome AF: 0.499 AC: 75768 AN: 151754 Hom.: 22328 Cov.: 30 AF XY: 0.502 AC XY: 37202 AN XY: 74128

African (AFR) AF: 0.179 AC: 7420 AN: 41384

American (AMR) AF: 0.541 AC: 8270 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3468

East Asian (EAS) AF: 0.372 AC: 1890 AN: 5076

South Asian (SAS) AF: 0.513 AC: 2460 AN: 4798

European-Finnish (FIN) AF: 0.704 AC: 7443 AN: 10574

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44191 AN: 67868

Other (OTH) AF: 0.529 AC: 1116 AN: 2110

Alfa AF: 0.586 Hom.: 63792

Bravo AF: 0.473

Asia WGS AF: 0.439 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.65
PhyloP100		-0.56
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: rs2855262; hg19: chr4-24801976; COSMIC: COSV66125735; COSMIC: COSV66125735;