rs17881180

Positions:

• chr21-31659974-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD1	NM_000454.5	c.72+133C>T		intron_variant		ENST00000270142.11	NP_000445.1
SOD1-DT	NR_187558.1	n.51G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD1	ENST00000270142.11	c.72+133C>T		intron_variant		1	NM_000454.5	ENSP00000270142.7
SOD1	ENST00000389995.4	c.15+190C>T		intron_variant		3		ENSP00000374645.4
SOD1	ENST00000470944.1	n.266C>T		non_coding_transcript_exon_variant	1/5	2
SOD1	ENST00000476106.5	n.149+133C>T		intron_variant		5

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

Gnomad4 AFR exome AF: 0.00975

Gnomad4 AMR exome AF: 0.0307

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.000348

Gnomad4 SAS exome AF: 0.0427

Gnomad4 FIN exome AF: 0.0562

Gnomad4 NFE exome AF: 0.0560

Gnomad4 OTH exome AF: 0.0457

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

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0500 Hom.: 28

Bravo AF: 0.0345

Asia WGS AF: 0.0170 AC: 60 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.9
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs17881180; hg19: chr21-33032287;