rs7827095

Positions:

• chr8-96226898-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006294.5(UQCRB):​c.*4157A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 453,472 control chromosomes in the GnomAD database, including 60,041 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (25536 hom., cov: 32)
  • Exomes 𝑓: 0.47 (34505 hom.)
• Consequence: UQCRB NM_006294.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31

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]

UQCRB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRB	NM_006294.5	c.*4157A>G		3_prime_UTR_variant	4/4	ENST00000287022.10	NP_006285.1
UQCRB	NM_001254752.2	c.*4207A>G		3_prime_UTR_variant	5/5		NP_001241681.1
UQCRB	NM_001199975.3	c.*4157A>G		3_prime_UTR_variant	5/5		NP_001186904.1
UQCRB	NR_045639.2	n.4798A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRB	ENST00000287022	c.*4157A>G		3_prime_UTR_variant	4/4	1	NM_006294.5	ENSP00000287022.5

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84103 AN: 151870 Hom.: 25480 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.514

GnomAD3 exomes AF: 0.447 AC: 57147 AN: 127902 Hom.: 13766 AF XY: 0.454 AC XY: 31813 AN XY: 70048

Gnomad AFR exome AF: 0.819

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.259

Gnomad SAS exome AF: 0.480

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.448

GnomAD4 exome AF: 0.469 AC: 141506 AN: 301484 Hom.: 34505 Cov.: 0 AF XY: 0.471 AC XY: 80876 AN XY: 171800

Gnomad4 AFR exome AF: 0.807

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.554 AC: 84210 AN: 151988 Hom.: 25536 Cov.: 32 AF XY: 0.547 AC XY: 40644 AN XY: 74260

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.510

Alfa AF: 0.497 Hom.: 10975

Bravo AF: 0.557

Asia WGS AF: 0.392 AC: 1360 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.047
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7827095; hg19: chr8-97239126;