chr21-31667461-TA-T

Position:

• chr21-31667461-TA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000454.5(SOD1):​c.357+89del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,001,226 control chromosomes in the GnomAD database, including 13,009 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1977 hom., cov: 31)
  • Exomes 𝑓: 0.11 (11032 hom.)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD1	NM_000454.5	c.357+89del		intron_variant		ENST00000270142.11	NP_000445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD1	ENST00000270142.11	c.357+89del		intron_variant		1	NM_000454.5	ENSP00000270142	P1
SOD1	ENST00000389995.4	c.300+89del		intron_variant		3		ENSP00000374645
SOD1	ENST00000470944.1	n.1285+89del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19335 AN: 152108 Hom.: 1972 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.108 AC: 92018 AN: 849000 Hom.: 11032 AF XY: 0.108 AC XY: 48093 AN XY: 447324

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.0706

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.0932

Gnomad4 NFE exome AF: 0.0534

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.127 AC: 19367 AN: 152226 Hom.: 1977 Cov.: 31 AF XY: 0.132 AC XY: 9843 AN XY: 74444

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.0649

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.0960

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0146 Hom.: 6

Bravo AF: 0.140

Asia WGS AF: 0.330 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3216079; hg19: chr21-33039774;