rs4816405

Positions:

• chr21-31660688-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+847C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,240 control chromosomes in the GnomAD database, including 1,699 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 0.12 (1699 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD1	NM_000454.5	c.72+847C>G		intron_variant		ENST00000270142.11	NP_000445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD1	ENST00000270142.11	c.72+847C>G		intron_variant		1	NM_000454.5	ENSP00000270142	P1
SOD1	ENST00000389995.4	c.15+904C>G		intron_variant		3		ENSP00000374645
SOD1	ENST00000470944.1	n.980C>G		non_coding_transcript_exon_variant	1/5	2
SOD1	ENST00000476106.5	n.149+847C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17612 AN: 152106 Hom.: 1699 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0649

Gnomad OTH AF: 0.0985

GnomAD4 exome AF: 0.125 AC: 2 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.116 AC: 17611 AN: 152224 Hom.: 1699 Cov.: 33 AF XY: 0.120 AC XY: 8969 AN XY: 74444

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.0649

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0864 Hom.: 97

Bravo AF: 0.126

Asia WGS AF: 0.324 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.8
DANN	Benign	0.73

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: rs4816405; hg19: chr21-33033001;