rs17882667

Variant names:

• chr4-24799530-G-C
• rs17882667
• NM_003102.4:c.9G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-24799530-G-C
• chr4-24799530-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003102.4(SOD3):​c.9G>C​(p.Ala3Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,599,408 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (119 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (118 hom.)
• Consequence: SOD3 NM_003102.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0970
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 4-24799530-G-C is Benign according to our data. Variant chr4-24799530-G-C is described in ClinVar as Benign. ClinVar VariationId is 775951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.097 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 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.9G>C	p.Ala3Ala	synonymous	Exon 2 of 2	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.9G>C	p.Ala3Ala	synonymous	Exon 2 of 2	ENSP00000371554.3	P08294
	SOD3	ENST00000880265.1		c.9G>C	p.Ala3Ala	synonymous	Exon 3 of 3	ENSP00000550324.1
	SOD3	ENST00000952028.1		c.9G>C	p.Ala3Ala	synonymous	Exon 3 of 3	ENSP00000622087.1

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3418 AN: 152190 Hom.: 120 Cov.: 33

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0225

GnomAD2 exomes AF: 0.00586 AC: 1319 AN: 224946 AF XY: 0.00466

Gnomad AFR exome AF: 0.0758

Gnomad AMR exome AF: 0.00542

Gnomad ASJ exome AF: 0.000104

Gnomad EAS exome AF: 0.000515

Gnomad FIN exome AF: 0.0000792

Gnomad NFE exome AF: 0.000566

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00266 AC: 3850 AN: 1447100 Hom.: 118 Cov.: 31 AF XY: 0.00241 AC XY: 1738 AN XY: 720288

African (AFR) AF: 0.0770 AC: 2573 AN: 33432

American (AMR) AF: 0.00636 AC: 283 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26052

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39628

South Asian (SAS) AF: 0.000245 AC: 21 AN: 85710

European-Finnish (FIN) AF: 0.0000738 AC: 3 AN: 40674

Middle Eastern (MID) AF: 0.00886 AC: 51 AN: 5756

European-Non Finnish (NFE) AF: 0.000460 AC: 511 AN: 1111170

Other (OTH) AF: 0.00660 AC: 397 AN: 60172

GnomAD4 genome AF: 0.0224 AC: 3412 AN: 152308 Hom.: 119 Cov.: 33 AF XY: 0.0216 AC XY: 1607 AN XY: 74476

African (AFR) AF: 0.0746 AC: 3101 AN: 41566

American (AMR) AF: 0.0135 AC: 206 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 68020

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.00163 Hom.: 7

Bravo AF: 0.0257

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17882667; hg19: chr4-24801152;