Variant chr8-96231406-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006294.5(UQCRB):c.259-274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,537,292 control chromosomes in the GnomAD database, including 1,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.029 ( 100 hom., cov: 33)

Exomes 𝑓: 0.041 ( 1331 hom. )

Consequence

UQCRB
NM_006294.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0130

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002295643).

BP6

Variant 8-96231406-G-A is Benign according to our data. Variant chr8-96231406-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 676767.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0286 (4348/152290) while in subpopulation NFE AF= 0.0457 (3109/68026). AF 95% confidence interval is 0.0444. There are 100 homozygotes in gnomad4. There are 1986 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UQCRB	NM_006294.5 linkuse as main transcript	c.259-274C>T		intron_variant		ENST00000287022.10
UQCRB	NM_001254752.2 linkuse as main transcript	c.368C>T	p.Pro123Leu	missense_variant	4/5
UQCRB	NM_001199975.3 linkuse as main transcript	c.163-274C>T		intron_variant
UQCRB	NR_045639.2 linkuse as main transcript	n.383C>T		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCRB	ENST00000287022.10 linkuse as main transcript	c.259-274C>T		intron_variant		1	NM_006294.5	P1	P14927-1

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4348

AN:

152172

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00750

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0212

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0457

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0275

AC:

3596

AN:

130938

Hom.:

AF XY:

0.0270

AC XY:

1927

AN XY:

71486

show subpopulations

Gnomad AFR exome

AF:

0.00896

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0466

Gnomad EAS exome

AF:

0.000188

Gnomad SAS exome

AF:

0.0146

Gnomad FIN exome

AF:

0.0227

Gnomad NFE exome

AF:

0.0447

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0407

AC:

56427

AN:

1385002

Hom.:

1331

Cov.:

AF XY:

0.0401

AC XY:

27391

AN XY:

683498

show subpopulations

Gnomad4 AFR exome

AF:

0.00703

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.0471

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.0129

Gnomad4 FIN exome

AF:

0.0254

Gnomad4 NFE exome

AF:

0.0467

Gnomad4 OTH exome

AF:

0.0345

GnomAD4 genome

AF:

0.0286

AC:

4348

AN:

152290

Hom.:

100

Cov.:

AF XY:

0.0267

AC XY:

1986

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00748

Gnomad4 AMR

AF:

0.0277

Gnomad4 ASJ

AF:

0.0478

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00995

Gnomad4 FIN

AF:

0.0212

Gnomad4 NFE

AF:

0.0457

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0340

Hom.:

Bravo

AF:

0.0276

TwinsUK

AF:

0.0464

AC:

172

ALSPAC

AF:

0.0501

AC:

193

ExAC

AF:

0.0124

AC:

419

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 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

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.1

DANN

Uncertain

0.99

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.027

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.19

MPC

0.079

ClinPred

0.0053

GERP RS

-1.2

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over