8-96230621-C-T

Position:

• chr8-96230621-C-T

Variant summary

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

The NM_006294.5(UQCRB):​c.*434G>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 0.34 in 455,480 control chromosomes in the GnomAD database, including 28,381 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 0.31 (8162 hom., cov: 32)
  • Exomes 𝑓: 0.36 (20219 hom.)
• Consequence: UQCRB NM_006294.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCRB	NM_006294.5	c.*434G>A		3_prime_UTR_variant	4/4	ENST00000287022.10
UQCRB	NM_001199975.3	c.*434G>A		3_prime_UTR_variant	5/5
UQCRB	NM_001254752.2	c.*484G>A		3_prime_UTR_variant	5/5
UQCRB	NR_045639.2	n.1075G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCRB	ENST00000287022.10	c.*434G>A		3_prime_UTR_variant	4/4	1	NM_006294.5	P1
UQCRB	ENST00000517603.5	c.*803G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46783 AN: 151836 Hom.: 8159 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.306

GnomAD3 exomes AF: 0.324 AC: 42327 AN: 130494 Hom.: 7405 AF XY: 0.334 AC XY: 23767 AN XY: 71234

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.344

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.357 AC: 108268 AN: 303526 Hom.: 20219 Cov.: 0 AF XY: 0.358 AC XY: 61916 AN XY: 172856

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.308 AC: 46790 AN: 151954 Hom.: 8162 Cov.: 32 AF XY: 0.309 AC XY: 22949 AN XY: 74258

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.304

Alfa AF: 0.302 Hom.: 1460

Bravo AF: 0.289

Asia WGS AF: 0.265 AC: 923 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.49

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: rs7836698; hg19: chr8-97242849;