8-96231561-G-C

Position:

• chr8-96231561-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006294.5(UQCRB):​c.258+213C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,405,970 control chromosomes in the GnomAD database, including 640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (37 hom., cov: 33)
  • Exomes 𝑓: 0.028 (603 hom.)
• Consequence: UQCRB NM_006294.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023460388).
• BP6: Variant 8-96231561-G-C is Benign according to our data. Variant chr8-96231561-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 676764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0202 (3072/152362) while in subpopulation NFE AF= 0.0308 (2094/68034). AF 95% confidence interval is 0.0297. There are 37 homozygotes in gnomad4. There are 1395 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCRB	NM_006294.5	c.258+213C>G		intron_variant		ENST00000287022.10
UQCRB	NM_001199975.3	c.162+213C>G		intron_variant
UQCRB	NM_001254752.2	c.259-46C>G		intron_variant
UQCRB	NR_045639.2	n.274-46C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCRB	ENST00000287022.10	c.258+213C>G		intron_variant		1	NM_006294.5	P1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3072 AN: 152244 Hom.: 37 Cov.: 33

Gnomad AFR AF: 0.00528

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0277

GnomAD3 exomes AF: 0.0180 AC: 2386 AN: 132302 Hom.: 35 AF XY: 0.0184 AC XY: 1323 AN XY: 72002

Gnomad AFR exome AF: 0.00358

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0170

Gnomad EAS exome AF: 0.0000912

Gnomad SAS exome AF: 0.00763

Gnomad FIN exome AF: 0.0291

Gnomad NFE exome AF: 0.0309

Gnomad OTH exome AF: 0.0217

GnomAD4 exome AF: 0.0283 AC: 35453 AN: 1253608 Hom.: 603 Cov.: 20 AF XY: 0.0275 AC XY: 17199 AN XY: 625342

Gnomad4 AFR exome AF: 0.00415

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.0000568

Gnomad4 SAS exome AF: 0.00798

Gnomad4 FIN exome AF: 0.0281

Gnomad4 NFE exome AF: 0.0328

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.0202 AC: 3072 AN: 152362 Hom.: 37 Cov.: 33 AF XY: 0.0187 AC XY: 1395 AN XY: 74512

Gnomad4 AFR AF: 0.00527

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0158

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.0288

Gnomad4 NFE AF: 0.0308

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0247 Hom.: 10

Bravo AF: 0.0193

TwinsUK AF: 0.0340 AC: 126

ALSPAC AF: 0.0311 AC: 120

ExAC AF: 0.00726 AC: 522

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.6
DANN	Benign	0.65
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	0.93	N
REVEL	Benign	0.022
Sift	Pathogenic	0.0	D
Vest4		0.24
ClinPred		0.025	T
GERP RS		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs77407648; hg19: chr8-97243789;