rs17878863

Variant names:

• chr4-24796196-A-G
• rs17878863
• NM_003102.4:c.-17+545A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-24796196-A-G
• chr4-24796196-A-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+545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 152,220 control chromosomes in the GnomAD database, including 400 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 0.060 (400 hom., cov: 31)
• Consequence: SOD3 NM_003102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003102.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD3	NM_003102.4	MANE Select	c.-17+545A>G		intron	N/A	NP_003093.2	A0A140VJU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD3	ENST00000382120.4	TSL:1 MANE Select	c.-17+545A>G		intron	N/A	ENSP00000371554.3	P08294
	SOD3	ENST00000880265.1		c.-37+545A>G		intron	N/A	ENSP00000550324.1
	SOD3	ENST00000952028.1		c.-111+545A>G		intron	N/A	ENSP00000622087.1

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9177 AN: 152102 Hom.: 400 Cov.: 31

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0603 AC: 9178 AN: 152220 Hom.: 400 Cov.: 31 AF XY: 0.0595 AC XY: 4427 AN XY: 74434

African (AFR) AF: 0.0142 AC: 589 AN: 41548

American (AMR) AF: 0.0487 AC: 744 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0210 AC: 101 AN: 4820

European-Finnish (FIN) AF: 0.130 AC: 1383 AN: 10604

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0879 AC: 5977 AN: 68000

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0280 Hom.: 38

Bravo AF: 0.0533

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.74
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17878863; hg19: chr4-24797818;