rs573544165

Variant names:

• chr21-31659686-C-G
• rs573544165
• ENST00000877328.1:c.-84C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-31659686-C-G
• chr21-31659686-C-A
• chr21-31659686-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The ENST00000389995.4(SOD1):​c.-84C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,424,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: SOD1 ENST00000389995.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.50
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000656 (10/152376) while in subpopulation EAS AF = 0.00174 (9/5182). AF 95% confidence interval is 0.000906. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000389995.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1-DT	NR_187558.1		n.339G>C		non_coding_transcript_exon	Exon 1 of 3
	SOD1	NM_000454.5	MANE Select	c.-84C>G		upstream_gene	N/A	NP_000445.1	P00441

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1	ENST00000877328.1		c.-84C>G		5_prime_UTR	Exon 1 of 4	ENSP00000547387.1
	SOD1	ENST00000928717.1		c.-84C>G		5_prime_UTR	Exon 1 of 5	ENSP00000598776.1
	SOD1	ENST00000928718.1		c.-84C>G		5_prime_UTR	Exon 1 of 5	ENSP00000598777.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000149 AC: 19 AN: 1271742 Hom.: 0 Cov.: 18 AF XY: 0.0000156 AC XY: 10 AN XY: 641214

African (AFR) AF: 0.00 AC: 0 AN: 29822

American (AMR) AF: 0.00 AC: 0 AN: 43754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24792

East Asian (EAS) AF: 0.000259 AC: 10 AN: 38564

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 0.00000531 AC: 5 AN: 942334

Other (OTH) AF: 0.0000554 AC: 3 AN: 54160

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152376 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74508

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Amyotrophic lateral sclerosis type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.13
DANN	Benign	0.46
PhyloP100		-2.5
PromoterAI		0.079	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs573544165; hg19: chr21-33031999;