4-24795242-C-G

Variant names:

• chr4-24795242-C-G
• rs699474
• ENST00000598411.1:c.-16-4264C>G

Variant summary

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

The ENST00000598411.1(SOD3):​c.-16-4264C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,226 control chromosomes in the GnomAD database, including 70,722 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 0.96 (70722 hom., cov: 31)
• Consequence: SOD3 ENST00000598411.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598411.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD3	ENST00000598411.1	TSL:5	c.-16-4264C>G		intron	N/A	ENSP00000472134.1

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146509 AN: 152108 Hom.: 70665 Cov.: 31

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.956

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

GnomAD4 genome AF: 0.963 AC: 146626 AN: 152226 Hom.: 70722 Cov.: 31 AF XY: 0.964 AC XY: 71736 AN XY: 74420

African (AFR) AF: 0.909 AC: 37737 AN: 41520

American (AMR) AF: 0.974 AC: 14903 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3375 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5140 AN: 5146

South Asian (SAS) AF: 0.959 AC: 4624 AN: 4820

European-Finnish (FIN) AF: 0.997 AC: 10587 AN: 10614

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67070 AN: 68040

Other (OTH) AF: 0.956 AC: 2018 AN: 2110

Alfa AF: 0.986 Hom.: 3435

Bravo AF: 0.960

Asia WGS AF: 0.973 AC: 3383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.54
PhyloP100		1.2
PromoterAI		0.015	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs699474; hg19: chr4-24796864;