ENST00000518876.1:n.304T>C

Variant names:

• chr8-96235241-A-G
• rs2643338
• ENST00000518876.1:n.304T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000518876.1(UQCRB):​n.304T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 590,358 control chromosomes in the GnomAD database, including 75,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (25520 hom., cov: 32)
  • Exomes 𝑓: 0.47 (49690 hom.)
• Consequence: UQCRB ENST00000518876.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0310
• Publications: 5 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-AS1 (HGNC:55521): (UQCRB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-96235241-A-G is Benign according to our data. Variant chr8-96235241-A-G is described in ClinVar as Benign. ClinVar VariationId is 684319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCRB	NM_006294.5	c.19+271T>C		intron_variant	Intron 1 of 3	ENST00000287022.10	NP_006285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCRB	ENST00000287022.10	c.19+271T>C		intron_variant	Intron 1 of 3	1	NM_006294.5	ENSP00000287022.5

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84144 AN: 151900 Hom.: 25469 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.468 AC: 205327 AN: 438340 Hom.: 49690 Cov.: 4 AF XY: 0.469 AC XY: 109082 AN XY: 232750

African (AFR) AF: 0.800 AC: 9712 AN: 12144

American (AMR) AF: 0.363 AC: 6806 AN: 18766

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 6361 AN: 13298

East Asian (EAS) AF: 0.293 AC: 8710 AN: 29760

South Asian (SAS) AF: 0.477 AC: 21799 AN: 45712

European-Finnish (FIN) AF: 0.472 AC: 13032 AN: 27618

Middle Eastern (MID) AF: 0.474 AC: 1019 AN: 2148

European-Non Finnish (NFE) AF: 0.478 AC: 126002 AN: 263694

Other (OTH) AF: 0.472 AC: 11886 AN: 25200

GnomAD4 genome AF: 0.554 AC: 84247 AN: 152018 Hom.: 25520 Cov.: 32 AF XY: 0.548 AC XY: 40677 AN XY: 74282

African (AFR) AF: 0.807 AC: 33461 AN: 41484

American (AMR) AF: 0.408 AC: 6245 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1767 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1426 AN: 5146

South Asian (SAS) AF: 0.451 AC: 2172 AN: 4816

European-Finnish (FIN) AF: 0.448 AC: 4727 AN: 10556

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

European-Non Finnish (NFE) AF: 0.482 AC: 32764 AN: 67940

Other (OTH) AF: 0.510 AC: 1072 AN: 2104

Alfa AF: 0.501 Hom.: 9549

Bravo AF: 0.557

Asia WGS AF: 0.394 AC: 1371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.54
PhyloP100		-0.031
PromoterAI		0.087	Neutral
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: rs2643338; hg19: chr8-97247469;