chr8-96231372-C-T

Position:

• chr8-96231372-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001254752.2(UQCRB):​c.395+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,541,476 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (24 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (24 hom.)
• Consequence: UQCRB NM_001254752.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-96231372-C-T is Benign according to our data. Variant chr8-96231372-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1213618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-96231372-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00997 (1518/152298) while in subpopulation AFR AF= 0.0347 (1443/41546). AF 95% confidence interval is 0.0332. There are 24 homozygotes in gnomad4. There are 694 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UQCRB	NM_006294.5	c.259-240G>A		intron_variant		ENST00000287022.10	NP_006285.1
UQCRB	NM_001254752.2	c.395+7G>A		splice_region_variant, intron_variant			NP_001241681.1
UQCRB	NM_001199975.3	c.163-240G>A		intron_variant			NP_001186904.1
UQCRB	NR_045639.2	n.417G>A		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UQCRB	ENST00000287022.10	c.259-240G>A		intron_variant		1	NM_006294.5	ENSP00000287022.5

Frequencies

GnomAD3 genomes AF: 0.00998 AC: 1519 AN: 152180 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00190 AC: 255 AN: 134196 Hom.: 5 AF XY: 0.00145 AC XY: 106 AN XY: 73090

Gnomad AFR exome AF: 0.0348

Gnomad AMR exome AF: 0.00106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000892

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000408

Gnomad OTH exome AF: 0.000738

GnomAD4 exome AF: 0.000954 AC: 1325 AN: 1389178 Hom.: 24 Cov.: 32 AF XY: 0.000779 AC XY: 534 AN XY: 685544

Gnomad4 AFR exome AF: 0.0351

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000505

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000334

Gnomad4 OTH exome AF: 0.00214

GnomAD4 genome AF: 0.00997 AC: 1518 AN: 152298 Hom.: 24 Cov.: 33 AF XY: 0.00932 AC XY: 694 AN XY: 74468

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00504 Hom.: 1

Bravo AF: 0.0114

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.33
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs112464633; hg19: chr8-97243600;