rs2070424

Variant names:

• chr21-31667007-A-G
• rs2070424
• NM_000454.5:c.240-251A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-31667007-A-G
• chr21-31667007-A-C
• chr21-31667007-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000454.5(SOD1):​c.240-251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 542,660 control chromosomes in the GnomAD database, including 8,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2061 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6206 hom.)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0290
• Publications: 61 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

ENSG00000273271 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 21-31667007-A-G is Benign according to our data. Variant chr21-31667007-A-G is described in ClinVar as Benign. ClinVar VariationId is 1253758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 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.240-251A>G		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.240-251A>G		intron	N/A	ENSP00000270142.7	P00441
	SOD1	ENST00000877332.1		c.378-251A>G		intron	N/A	ENSP00000547391.1
	SOD1	ENST00000877328.1		c.303-251A>G		intron	N/A	ENSP00000547387.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20286 AN: 152086 Hom.: 2056 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.125 AC: 48871 AN: 390456 Hom.: 6206 Cov.: 0 AF XY: 0.126 AC XY: 26017 AN XY: 206944

African (AFR) AF: 0.175 AC: 1977 AN: 11272

American (AMR) AF: 0.272 AC: 4532 AN: 16662

Ashkenazi Jewish (ASJ) AF: 0.0808 AC: 978 AN: 12106

East Asian (EAS) AF: 0.524 AC: 13599 AN: 25936

South Asian (SAS) AF: 0.187 AC: 7794 AN: 41612

European-Finnish (FIN) AF: 0.0979 AC: 2281 AN: 23300

Middle Eastern (MID) AF: 0.0596 AC: 102 AN: 1710

European-Non Finnish (NFE) AF: 0.0634 AC: 14918 AN: 235160

Other (OTH) AF: 0.119 AC: 2690 AN: 22698

GnomAD4 genome AF: 0.133 AC: 20318 AN: 152204 Hom.: 2061 Cov.: 32 AF XY: 0.138 AC XY: 10253 AN XY: 74404

African (AFR) AF: 0.179 AC: 7449 AN: 41518

American (AMR) AF: 0.205 AC: 3136 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2655 AN: 5166

South Asian (SAS) AF: 0.208 AC: 998 AN: 4806

European-Finnish (FIN) AF: 0.0993 AC: 1054 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0651 AC: 4431 AN: 68020

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.0914 Hom.: 1307

Bravo AF: 0.147

Asia WGS AF: 0.332 AC: 1153 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	-0.79
CADD	Benign	6.6
DANN	Benign	0.82
PhyloP100		-0.029
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: rs2070424; hg19: chr21-33039320;