chr20-41084548-A-G
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_003286.4(TOP1):c.594A>G(p.Glu198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,570,354 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 6 hom. )
Consequence
TOP1
NM_003286.4 synonymous
NM_003286.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.09
Genes affected
TOP1 (HGNC:11986): (DNA topoisomerase I) This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 20-41084548-A-G is Benign according to our data. Variant chr20-41084548-A-G is described in ClinVar as [Benign]. Clinvar id is 713745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.09 with no splicing effect.
BS2
?
High AC in GnomAd at 247 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TOP1 | NM_003286.4 | c.594A>G | p.Glu198= | synonymous_variant | 8/21 | ENST00000361337.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TOP1 | ENST00000361337.3 | c.594A>G | p.Glu198= | synonymous_variant | 8/21 | 1 | NM_003286.4 | P1 | |
TOP1 | ENST00000681058.1 | n.748A>G | non_coding_transcript_exon_variant | 8/20 | |||||
TOP1 | ENST00000681392.1 | n.1714A>G | non_coding_transcript_exon_variant | 4/18 | |||||
TOP1 | ENST00000681113.1 | c.594A>G | p.Glu198= | synonymous_variant, NMD_transcript_variant | 8/23 |
Frequencies
GnomAD3 genomes ? AF: 0.00162 AC: 247AN: 152252Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00174 AC: 334AN: 191736Hom.: 2 AF XY: 0.00172 AC XY: 175AN XY: 102026
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GnomAD4 exome AF: 0.00237 AC: 3362AN: 1417984Hom.: 6 Cov.: 29 AF XY: 0.00221 AC XY: 1552AN XY: 701806
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
TOP1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 21, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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