rs17884057

Variant names:

• chr21-31664501-GAGA-G
• rs17884057
• NM_000454.5:c.169+622_169+624delAGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000454.5(SOD1):​c.169+622_169+624delAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 155,870 control chromosomes in the GnomAD database, including 1,532 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1494 hom., cov: 29)
  • Exomes 𝑓: 0.13 (38 hom.)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432

Genes affected

SOD1 (HGNC:11179): (superoxide dismutase 1) The protein encoded by this gene binds copper and zinc ions and is one of two isozymes responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic protein, acting as a homodimer to convert naturally-occuring but harmful superoxide radicals to molecular oxygen and hydrogen peroxide. The other isozyme is a mitochondrial protein. In addition, this protein contains an antimicrobial peptide that displays antibacterial, antifungal, and anti-MRSA activity against E. coli, E. faecalis, S. aureus, S. aureus MRSA LPV+, S. agalactiae, and yeast C. krusei. Mutations in this gene have been implicated as causes of familial amyotrophic lateral sclerosis. Rare transcript variants have been reported for this gene. [provided by RefSeq, Jul 2020]

ENSG00000238390 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD1	NM_000454.5	c.169+622_169+624delAGA		intron_variant	Intron 2 of 4	ENST00000270142.11	NP_000445.1
LOC124900469	XR_007067939.1	n.*20_*22delAGA		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD1	ENST00000270142.11	c.169+616_169+618delAGA		intron_variant	Intron 2 of 4	1	NM_000454.5	ENSP00000270142.7

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19512 AN: 152024 Hom.: 1494 Cov.: 29

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.127 AC: 473 AN: 3728 Hom.: 38 AF XY: 0.126 AC XY: 240 AN XY: 1904

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 24

Gnomad4 AMR exome AF: 0.0898 AC: 51 AN: 568

Gnomad4 ASJ exome AF: 0.231 AC: 6 AN: 26

Gnomad4 EAS exome AF: 0.0116 AC: 1 AN: 86

Gnomad4 SAS exome AF: 0.155 AC: 39 AN: 252

Gnomad4 FIN exome AF: 0.107 AC: 60 AN: 562

Gnomad4 NFE exome AF: 0.144 AC: 303 AN: 2106

Gnomad4 Remaining exome AF: 0.125 AC: 12 AN: 96

GnomAD4 genome AF: 0.128 AC: 19505 AN: 152142 Hom.: 1494 Cov.: 29 AF XY: 0.128 AC XY: 9520 AN XY: 74388

Gnomad4 AFR AF: 0.0562 AC: 0.0562431 AN: 0.0562431

Gnomad4 AMR AF: 0.131 AC: 0.131334 AN: 0.131334

Gnomad4 ASJ AF: 0.272 AC: 0.272072 AN: 0.272072

Gnomad4 EAS AF: 0.00675 AC: 0.00674634 AN: 0.00674634

Gnomad4 SAS AF: 0.144 AC: 0.143867 AN: 0.143867

Gnomad4 FIN AF: 0.151 AC: 0.151057 AN: 0.151057

Gnomad4 NFE AF: 0.167 AC: 0.167417 AN: 0.167417

Gnomad4 OTH AF: 0.132 AC: 0.13245 AN: 0.13245

Alfa AF: 0.144 Hom.: 210

Bravo AF: 0.122

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism (auto)

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: rs17884057; hg19: chr21-33036814;