21-31659722-T-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000454.5(SOD1):c.-48T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,593,380 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000454.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SOD1 | ENST00000270142 | c.-48T>A | 5_prime_UTR_variant | Exon 1 of 5 | 1 | NM_000454.5 | ENSP00000270142.7 | |||
SOD1 | ENST00000389995 | c.-48T>A | 5_prime_UTR_variant | Exon 1 of 5 | 3 | ENSP00000374645.4 | ||||
SOD1 | ENST00000470944.1 | n.14T>A | non_coding_transcript_exon_variant | Exon 1 of 5 | 2 | |||||
SOD1 | ENST00000476106.5 | n.30T>A | non_coding_transcript_exon_variant | Exon 1 of 5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00524 AC: 798AN: 152234Hom.: 11 Cov.: 33
GnomAD3 exomes AF: 0.00150 AC: 374AN: 249208Hom.: 5 AF XY: 0.00115 AC XY: 155AN XY: 135200
GnomAD4 exome AF: 0.000586 AC: 844AN: 1441028Hom.: 13 Cov.: 27 AF XY: 0.000536 AC XY: 385AN XY: 718126
GnomAD4 genome AF: 0.00525 AC: 800AN: 152352Hom.: 11 Cov.: 33 AF XY: 0.00511 AC XY: 381AN XY: 74500
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 1 Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at