chr16-58001290-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000698445.1(USB1):c.-194C>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 0.0117 in 679,862 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.011 ( 15 hom., cov: 33)
Exomes 𝑓: 0.012 ( 58 hom. )
Consequence
USB1
ENST00000698445.1 5_prime_UTR
ENST00000698445.1 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.815
Genes affected
USB1 (HGNC:25792): (U6 snRNA biogenesis phosphodiesterase 1) This gene encodes a protein with several conserved domains, however, its exact function is not known. Mutations in this gene are associated with poikiloderma with neutropenia (PN), which shows phenotypic overlap with Rothmund-Thomson syndrome (RTS) caused by mutations in the RECQL4 gene. It is believed that this gene product interacts with RECQL4 protein via SMAD4 proteins, explaining the partial clinical overlap between PN and RTS. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 16-58001290-C-G is Benign according to our data. Variant chr16-58001290-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1800912.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0105 (1602/152272) while in subpopulation AMR AF= 0.022 (336/15298). AF 95% confidence interval is 0.02. There are 15 homozygotes in gnomad4. There are 831 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USB1 | NM_001330568.2 | c.-55-1189C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USB1 | ENST00000698445.1 | c.-194C>G | 5_prime_UTR_variant | 1/6 | |||||
USB1 | ENST00000561743.5 | c.-55-1189C>G | intron_variant | 3 | P1 | ||||
USB1 | ENST00000698444.1 | c.-55-1189C>G | intron_variant | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0105 AC: 1596AN: 152154Hom.: 14 Cov.: 33
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GnomAD4 exome AF: 0.0120 AC: 6330AN: 527590Hom.: 58 AF XY: 0.0121 AC XY: 3388AN XY: 279382
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GnomAD4 genome ? AF: 0.0105 AC: 1602AN: 152272Hom.: 15 Cov.: 33 AF XY: 0.0112 AC XY: 831AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 16, 2021 | See Variant Classification Assertion Criteria. - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at