8-96226898-T-C

Variant names:

• chr8-96226898-T-C
• rs7827095
• NM_006294.5:c.*4157A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency nuclear type 3

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006294.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB	NM_006294.5	MANE Select	c.*4157A>G		3_prime_UTR	Exon 4 of 4	NP_006285.1
	UQCRB	NR_045639.2		n.4798A>G		non_coding_transcript_exon	Exon 5 of 5
	UQCRB	NM_001254752.2		c.*4207A>G		3_prime_UTR	Exon 5 of 5	NP_001241681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB	ENST00000287022.10	TSL:1 MANE Select	c.*4157A>G		3_prime_UTR	Exon 4 of 4	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

GnomAD2 exomes AF: 0.447 AC: 57147 AN: 127902 AF XY: 0.454

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 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

African (AFR) AF: 0.807 AC: 6896 AN: 8546

American (AMR) AF: 0.335 AC: 9122 AN: 27244

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 5150 AN: 10776

East Asian (EAS) AF: 0.258 AC: 2375 AN: 9208

South Asian (SAS) AF: 0.478 AC: 28485 AN: 59534

European-Finnish (FIN) AF: 0.474 AC: 5859 AN: 12356

Middle Eastern (MID) AF: 0.490 AC: 563 AN: 1148

European-Non Finnish (NFE) AF: 0.482 AC: 76413 AN: 158646

Other (OTH) AF: 0.474 AC: 6643 AN: 14026

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

African (AFR) AF: 0.810 AC: 33572 AN: 41472

American (AMR) AF: 0.408 AC: 6245 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5170

South Asian (SAS) AF: 0.450 AC: 2171 AN: 4820

European-Finnish (FIN) AF: 0.447 AC: 4707 AN: 10526

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32628 AN: 67922

Other (OTH) AF: 0.510 AC: 1078 AN: 2112

Alfa AF: 0.497 Hom.: 11928

Bravo AF: 0.557

Asia WGS AF: 0.392 AC: 1360 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.047
DANN	Benign	0.44
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7827095; hg19: chr8-97239126;