chr8-96235630-C-A

Variant names:

• chr8-96235630-C-A
• rs73698550
• ENST00000520575.2:n.271+69C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000520575.2(UQCRB-AS1):​n.271+69C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,497,082 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (45 hom.)
• Consequence: UQCRB-AS1 ENST00000520575.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.329
• Publications: 1 publications found

Genes affected

UQCRB-AS1 (HGNC:55521): (UQCRB antisense RNA 1)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 8-96235630-C-A is Benign according to our data. Variant chr8-96235630-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 675850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1896/152346) while in subpopulation AFR AF = 0.0433 (1801/41576). AF 95% confidence interval is 0.0417. There are 40 homozygotes in GnomAd4. There are 899 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520575.2. 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-AS1	NR_183274.1		n.269+69C>A		intron	N/A
	UQCRB-AS1	NR_183275.1		n.269+69C>A		intron	N/A
	UQCRB	NM_006294.5	MANE Select	c.-100G>T		upstream_gene	N/A	NP_006285.1	P14927-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB-AS1	ENST00000520575.2	TSL:2	n.271+69C>A		intron	N/A
	UQCRB-AS1	ENST00000727541.1		n.574+69C>A		intron	N/A
	UQCRB	ENST00000287022.10	TSL:1 MANE Select	c.-100G>T		upstream_gene	N/A	ENSP00000287022.5	P14927-1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1894 AN: 152228 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.00339 AC: 831 AN: 245472 AF XY: 0.00272

Gnomad AFR exome AF: 0.0450

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000209

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.00136 AC: 1825 AN: 1344736 Hom.: 45 Cov.: 21 AF XY: 0.00120 AC XY: 810 AN XY: 675756

African (AFR) AF: 0.0441 AC: 1368 AN: 31010

American (AMR) AF: 0.00282 AC: 125 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 39128

South Asian (SAS) AF: 0.000131 AC: 11 AN: 83656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53020

Middle Eastern (MID) AF: 0.00456 AC: 23 AN: 5048

European-Non Finnish (NFE) AF: 0.000134 AC: 135 AN: 1006832

Other (OTH) AF: 0.00290 AC: 163 AN: 56296

GnomAD4 genome AF: 0.0124 AC: 1896 AN: 152346 Hom.: 40 Cov.: 33 AF XY: 0.0121 AC XY: 899 AN XY: 74500

African (AFR) AF: 0.0433 AC: 1801 AN: 41576

American (AMR) AF: 0.00438 AC: 67 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68040

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.00777 Hom.: 6

Bravo AF: 0.0139

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.70
DANN	Benign	0.89
PhyloP100		-0.33
PromoterAI		-0.030	Neutral
Mutation Taster		=300/0	polymorphism

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: rs73698550; hg19: chr8-97247858;