dbSNP rs17884057: SOD1:c.169+622_169+624delAGA (chr21-31664501-GAGA-G) – ACMG Classification: Benign (-8 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.432

Publications

5 publications found

Variant links:

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: AD, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
spastic tetraplegia and axial hypotonia, progressive
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SOD1 links:

ENSG00000238390 (HGNC:):

ENSG00000238390 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.169+622_169+624delAGA		intron_variant	Intron 2 of 4	ENST00000270142.11	NP_000445.1
LOC124900469	XR_007067939.1 link	n.20_22delAGA		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD1	ENST00000270142.11 link	c.169+616_169+618delAGA		intron_variant	Intron 2 of 4	1	NM_000454.5	ENSP00000270142.7		P00441

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19512

AN:

152024

Hom.:

1494

Cov.:

show subpopulations

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.:

AF XY:

0.126

AC XY:

240

AN XY:

1904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0898

AC:

AN:

568

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

AN:

East Asian (EAS)

AF:

0.0116

AC:

AN:

South Asian (SAS)

AF:

0.155

AC:

AN:

252

European-Finnish (FIN)

AF:

0.107

AC:

AN:

562

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.144

AC:

303

AN:

2106

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.128

AC:

19505

AN:

152142

Hom.:

1494

Cov.:

AF XY:

0.128

AC XY:

9520

AN XY:

74388

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11378

AN:

67962

Other (OTH)

AF:

0.132

AC:

280

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

810

1620

2430

3240

4050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over