rs17880362

Variant names:

• chr4-24798079-C-T
• rs17880362
• NM_003102.4:c.-16-1427C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003102.4(SOD3):​c.-16-1427C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 148,600 control chromosomes in the GnomAD database, including 7 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 0.010 (7 hom., cov: 32)
• Consequence: SOD3 NM_003102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD3	NM_003102.4	c.-16-1427C>T		intron_variant	Intron 1 of 1	ENST00000382120.4	NP_003093.2
SOD3	XR_427488.2	n.80-1427C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD3	ENST00000382120.4	c.-16-1427C>T		intron_variant	Intron 1 of 1	1	NM_003102.4	ENSP00000371554.3
SOD3	ENST00000598411.1	c.-16-1427C>T		intron_variant	Intron 2 of 2	5		ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1504 AN: 148492 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00288

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.00604

Gnomad FIN AF: 0.00833

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.00976

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

GnomAD4 genome AF: 0.0101 AC: 1504 AN: 148600 Hom.: 7 Cov.: 32 AF XY: 0.00944 AC XY: 686 AN XY: 72672

African (AFR) AF: 0.00287 AC: 110 AN: 38286

American (AMR) AF: 0.0137 AC: 207 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5172

South Asian (SAS) AF: 0.00605 AC: 29 AN: 4792

European-Finnish (FIN) AF: 0.00833 AC: 88 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0147 AC: 1001 AN: 67908

Other (OTH) AF: 0.00965 AC: 20 AN: 2072

Alfa AF: 0.0123 Hom.: 21

Bravo AF: 0.00977

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.31
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs17880362; hg19: chr4-24799701;