8-96231406-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_006294.5(UQCRB):c.259-274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,537,292 control chromosomes in the GnomAD database, including 1,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.029 ( 100 hom., cov: 33)
Exomes 𝑓: 0.041 ( 1331 hom. )
Consequence
UQCRB
NM_006294.5 intron
NM_006294.5 intron
Scores
2
1
12
Clinical Significance
Conservation
PhyloP100: -0.0130
Genes affected
UQCRB (HGNC:12582): (ubiquinol-cytochrome c reductase binding protein) This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. This protein plays an important role in hypoxia-induced angiogenesis through mitochondrial reactive oxygen species-mediated signaling. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X. [provided by RefSeq, Dec 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 (MetaRNN=0.002295643).
BP6
Variant 8-96231406-G-A is Benign according to our data. Variant chr8-96231406-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 676767.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0286 (4348/152290) while in subpopulation NFE AF= 0.0457 (3109/68026). AF 95% confidence interval is 0.0444. There are 100 homozygotes in gnomad4. There are 1986 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 100 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UQCRB | NM_006294.5 | c.259-274C>T | intron_variant | ENST00000287022.10 | |||
UQCRB | NM_001254752.2 | c.368C>T | p.Pro123Leu | missense_variant | 4/5 | ||
UQCRB | NM_001199975.3 | c.163-274C>T | intron_variant | ||||
UQCRB | NR_045639.2 | n.383C>T | non_coding_transcript_exon_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UQCRB | ENST00000287022.10 | c.259-274C>T | intron_variant | 1 | NM_006294.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0286 AC: 4348AN: 152172Hom.: 100 Cov.: 33
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GnomAD3 exomes AF: 0.0275 AC: 3596AN: 130938Hom.: 76 AF XY: 0.0270 AC XY: 1927AN XY: 71486
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GnomAD4 exome AF: 0.0407 AC: 56427AN: 1385002Hom.: 1331 Cov.: 32 AF XY: 0.0401 AC XY: 27391AN XY: 683498
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GnomAD4 genome AF: 0.0286 AC: 4348AN: 152290Hom.: 100 Cov.: 33 AF XY: 0.0267 AC XY: 1986AN XY: 74472
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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 | Jun 16, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Vest4
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at