rs6650814

chr21-31660675-C-Achr21-31660675-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000454.5(SOD1):c.72+834C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,202 control chromosomes in the GnomAD database, including 1,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1691 hom., cov: 33)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD1	NM_000454.5	c.72+834C>A		intron_variant		ENST00000270142.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD1	ENST00000270142.11	c.72+834C>A		intron_variant		1	NM_000454.5	P1
SOD1	ENST00000389995.4	c.15+891C>A		intron_variant		3
SOD1	ENST00000470944.1	n.967C>A		non_coding_transcript_exon_variant	1/5	2
SOD1	ENST00000476106.5	n.149+834C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16524 AN: 152070 Hom.: 1673 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0940

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0741

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.109 AC: 16588 AN: 152188 Hom.: 1691 Cov.: 33 AF XY: 0.107 AC XY: 7933 AN XY: 74434

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0940

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0365 Hom.: 39

Bravo AF: 0.114

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.0
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs6650814; hg19: chr21-33032988;