chr8-96230621-C-T

Variant names:

• chr8-96230621-C-T
• rs7836698
• NM_006294.5:c.*434G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB	NM_006294.5	MANE Select	c.*434G>A		3_prime_UTR	Exon 4 of 4	NP_006285.1	P14927-1
	UQCRB	NM_001254752.2		c.*484G>A		3_prime_UTR	Exon 5 of 5	NP_001241681.1	P14927-2
	UQCRB	NM_001199975.3		c.*434G>A		3_prime_UTR	Exon 5 of 5	NP_001186904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB	ENST00000287022.10	TSL:1 MANE Select	c.*434G>A		3_prime_UTR	Exon 4 of 4	ENSP00000287022.5	P14927-1
	UQCRB	ENST00000517603.5	TSL:1	n.*803G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000430672.1	E5RIT7
	UQCRB	ENST00000517603.5	TSL:1	n.*803G>A		3_prime_UTR	Exon 5 of 5	ENSP00000430672.1	E5RIT7

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

GnomAD2 exomes AF: 0.324 AC: 42327 AN: 130494 AF XY: 0.334

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 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

African (AFR) AF: 0.154 AC: 1337 AN: 8662

American (AMR) AF: 0.261 AC: 7141 AN: 27308

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 3391 AN: 10856

East Asian (EAS) AF: 0.181 AC: 1677 AN: 9266

South Asian (SAS) AF: 0.344 AC: 20545 AN: 59668

European-Finnish (FIN) AF: 0.425 AC: 5284 AN: 12442

Middle Eastern (MID) AF: 0.333 AC: 386 AN: 1160

European-Non Finnish (NFE) AF: 0.397 AC: 63551 AN: 159998

Other (OTH) AF: 0.350 AC: 4956 AN: 14166

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

African (AFR) AF: 0.156 AC: 6467 AN: 41470

American (AMR) AF: 0.282 AC: 4304 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3470

East Asian (EAS) AF: 0.189 AC: 974 AN: 5166

South Asian (SAS) AF: 0.315 AC: 1523 AN: 4830

European-Finnish (FIN) AF: 0.404 AC: 4253 AN: 10518

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26917 AN: 67924

Other (OTH) AF: 0.304 AC: 640 AN: 2106

Alfa AF: 0.298 Hom.: 1470

Bravo AF: 0.289

Asia WGS AF: 0.265 AC: 923 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.49
PhyloP100		-1.6
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: rs7836698; hg19: chr8-97242849;