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
• Publications: 5 publications found

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]

SOD1 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 1

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
• spastic tetraplegia and axial hypotonia, progressive

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000454.5. 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
	SOD1	NM_000454.5	MANE Select	c.169+622_169+624delAGA		intron	N/A	NP_000445.1	P00441

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1	ENST00000270142.11	TSL:1 MANE Select	c.169+616_169+618delAGA		intron	N/A	ENSP00000270142.7	P00441
	SOD1	ENST00000877332.1		c.307+616_307+618delAGA		intron	N/A	ENSP00000547391.1
	SOD1	ENST00000877328.1		c.233-1947_233-1945delAGA		intron	N/A	ENSP00000547387.1

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

African (AFR) AF: 0.00 AC: 0 AN: 24

American (AMR) AF: 0.0898 AC: 51 AN: 568

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6 AN: 26

East Asian (EAS) AF: 0.0116 AC: 1 AN: 86

South Asian (SAS) AF: 0.155 AC: 39 AN: 252

European-Finnish (FIN) AF: 0.107 AC: 60 AN: 562

Middle Eastern (MID) AF: 0.125 AC: 1 AN: 8

European-Non Finnish (NFE) AF: 0.144 AC: 303 AN: 2106

Other (OTH) 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

African (AFR) AF: 0.0562 AC: 2336 AN: 41534

American (AMR) AF: 0.131 AC: 2006 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3466

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5188

South Asian (SAS) AF: 0.144 AC: 692 AN: 4810

European-Finnish (FIN) AF: 0.151 AC: 1600 AN: 10592

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11378 AN: 67962

Other (OTH) AF: 0.132 AC: 280 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
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

Other links and lift over

dbSNP: rs17884057; hg19: chr21-33036814;