21-31659744-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_000454.5(SOD1):c.-26A>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 0.0000304 in 1,613,630 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
SOD1
NM_000454.5 5_prime_UTR
NM_000454.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0160
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 21-31659744-A-G is Benign according to our data. Variant chr21-31659744-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 339667.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SOD1 | NM_000454.5 | c.-26A>G | 5_prime_UTR_variant | 1/5 | ENST00000270142.11 | NP_000445.1 | ||
SOD1-DT | NR_187558.1 | n.281T>C | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SOD1 | ENST00000270142.11 | c.-26A>G | 5_prime_UTR_variant | 1/5 | 1 | NM_000454.5 | ENSP00000270142.7 | |||
SOD1 | ENST00000389995.4 | c.-26A>G | 5_prime_UTR_variant | 1/5 | 3 | ENSP00000374645.4 | ||||
SOD1 | ENST00000470944.1 | n.36A>G | non_coding_transcript_exon_variant | 1/5 | 2 | |||||
SOD1 | ENST00000476106.5 | n.52A>G | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000919 AC: 23AN: 250160Hom.: 0 AF XY: 0.0000959 AC XY: 13AN XY: 135580
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461264Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 726986
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GnomAD4 genome AF: 0.00000656 AC: 1AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74520
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Amyotrophic lateral sclerosis type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at