rs800444

chr4-24798241-G-Achr4-24798241-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003102.4(SOD3):c.-16-1265G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 152,162 control chromosomes in the GnomAD database, including 69,048 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 0.95 (69048 hom., cov: 29)
• Consequence: SOD3 NM_003102.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD3	NM_003102.4	c.-16-1265G>A		intron_variant		ENST00000382120.4
SOD3	XR_427488.2	n.80-1265G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD3	ENST00000382120.4	c.-16-1265G>A		intron_variant		1	NM_003102.4	P1
SOD3	ENST00000598411.1	c.-16-1265G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.952 AC: 144782 AN: 152044 Hom.: 69004 Cov.: 29

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.952 AC: 144885 AN: 152162 Hom.: 69048 Cov.: 29 AF XY: 0.953 AC XY: 70919 AN XY: 74402

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.961

Gnomad4 OTH AF: 0.961

Alfa AF: 0.955 Hom.: 18080

Bravo AF: 0.952

Asia WGS AF: 0.981 AC: 3412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.97
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs800444; hg19: chr4-24799863;