rs10504961

Positions:

• chr8-96227901-C-T

Variant summary

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

The ENST00000287022.10(UQCRB):​c.*3154G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 453,846 control chromosomes in the GnomAD database, including 46,486 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 0.46 (16300 hom., cov: 33)
  • Exomes 𝑓: 0.44 (30186 hom.)
• Consequence: UQCRB ENST00000287022.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRB	NM_006294.5	c.*3154G>A		3_prime_UTR_variant	4/4	ENST00000287022.10	NP_006285.1
UQCRB	NM_001199975.3	c.*3154G>A		3_prime_UTR_variant	5/5		NP_001186904.1
UQCRB	NM_001254752.2	c.*3204G>A		3_prime_UTR_variant	5/5		NP_001241681.1
UQCRB	NR_045639.2	n.3795G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRB	ENST00000287022.10	c.*3154G>A		3_prime_UTR_variant	4/4	1	NM_006294.5	ENSP00000287022	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69425 AN: 151952 Hom.: 16283 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.449

GnomAD3 exomes AF: 0.407 AC: 53040 AN: 130448 Hom.: 11525 AF XY: 0.414 AC XY: 29488 AN XY: 71202

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.316

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.401

Gnomad FIN exome AF: 0.475

Gnomad NFE exome AF: 0.473

Gnomad OTH exome AF: 0.431

GnomAD4 exome AF: 0.439 AC: 132417 AN: 301776 Hom.: 30186 Cov.: 0 AF XY: 0.437 AC XY: 75233 AN XY: 171988

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.457 AC: 69481 AN: 152070 Hom.: 16300 Cov.: 33 AF XY: 0.453 AC XY: 33674 AN XY: 74354

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.445

Alfa AF: 0.480 Hom.: 5590

Bravo AF: 0.449

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.52

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: rs10504961; hg19: chr8-97240129;