8-96231506-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006294.5(UQCRB):c.258+268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,531,438 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0062 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00062 ( 7 hom. )
Consequence
UQCRB
NM_006294.5 intron
NM_006294.5 intron
Scores
15
Clinical Significance
Conservation
PhyloP100: -2.78
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0034092069).
BP6
Variant 8-96231506-C-T is Benign according to our data. Variant chr8-96231506-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 811923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-96231506-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00616 (938/152338) while in subpopulation AFR AF= 0.0204 (848/41582). AF 95% confidence interval is 0.0193. There are 6 homozygotes in gnomad4. There are 438 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UQCRB | NM_006294.5 | c.258+268G>A | intron_variant | ENST00000287022.10 | |||
UQCRB | NM_001254752.2 | c.268G>A | p.Val90Ile | missense_variant | 4/5 | ||
UQCRB | NM_001199975.3 | c.162+268G>A | intron_variant | ||||
UQCRB | NR_045639.2 | n.283G>A | non_coding_transcript_exon_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UQCRB | ENST00000287022.10 | c.258+268G>A | intron_variant | 1 | NM_006294.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00615 AC: 936AN: 152220Hom.: 6 Cov.: 33
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GnomAD3 exomes AF: 0.00157 AC: 203AN: 129226Hom.: 3 AF XY: 0.00119 AC XY: 84AN XY: 70500
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GnomAD4 exome AF: 0.000619 AC: 853AN: 1379100Hom.: 7 Cov.: 30 AF XY: 0.000547 AC XY: 372AN XY: 680646
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GnomAD4 genome AF: 0.00616 AC: 938AN: 152338Hom.: 6 Cov.: 33 AF XY: 0.00588 AC XY: 438AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Mitochondrial complex III deficiency nuclear type 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 05, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 07, 2018 | - - |
UQCRB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 04, 2019 | 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
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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
Benign
T;D
Sift4G
Benign
T;T
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
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