rs17881180

Variant names:

• chr21-31659974-C-T
• rs17881180
• NM_000454.5:c.72+133C>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.72+133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 816,744 control chromosomes in the GnomAD database, including 1,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (147 hom., cov: 33)
  • Exomes 𝑓: 0.050 (1029 hom.)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0390
• Publications: 4 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-DT (HGNC:55683): (SOD1 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 21-31659974-C-T is Benign according to our data. Variant chr21-31659974-C-T is described in ClinVar as Benign. ClinVar VariationId is 1257173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0561 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1	NM_000454.5	MANE Select	c.72+133C>T		intron	N/A	NP_000445.1
	SOD1-DT	NR_187558.1		n.51G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1	ENST00000270142.11	TSL:1 MANE Select	c.72+133C>T		intron	N/A	ENSP00000270142.7
	SOD1	ENST00000470944.1	TSL:2	n.266C>T		non_coding_transcript_exon	Exon 1 of 5
	SOD1	ENST00000389995.4	TSL:3	c.15+190C>T		intron	N/A	ENSP00000374645.4

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5775 AN: 151884 Hom.: 147 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0497 AC: 33018 AN: 664752 Hom.: 1029 Cov.: 9 AF XY: 0.0501 AC XY: 17343 AN XY: 346416

African (AFR) AF: 0.00975 AC: 138 AN: 14148

American (AMR) AF: 0.0307 AC: 659 AN: 21458

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 488 AN: 15084

East Asian (EAS) AF: 0.000348 AC: 10 AN: 28720

South Asian (SAS) AF: 0.0427 AC: 2240 AN: 52400

European-Finnish (FIN) AF: 0.0562 AC: 1720 AN: 30624

Middle Eastern (MID) AF: 0.0417 AC: 101 AN: 2424

European-Non Finnish (NFE) AF: 0.0560 AC: 26163 AN: 467092

Other (OTH) AF: 0.0457 AC: 1499 AN: 32802

GnomAD4 genome AF: 0.0380 AC: 5774 AN: 151992 Hom.: 147 Cov.: 33 AF XY: 0.0373 AC XY: 2775 AN XY: 74320

African (AFR) AF: 0.0105 AC: 437 AN: 41536

American (AMR) AF: 0.0352 AC: 538 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3468

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5164

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4824

European-Finnish (FIN) AF: 0.0469 AC: 492 AN: 10498

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0576 AC: 3913 AN: 67916

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0500 Hom.: 28

Bravo AF: 0.0345

Asia WGS AF: 0.0170 AC: 60 AN: 3464

ClinVar

ClinVar submissions as Germline

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	-0.65
CADD	Benign	7.9
DANN	Benign	0.95
PhyloP100		-0.039
PromoterAI		-0.0016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17881180; hg19: chr21-33032287;