8-96235770-A-T

Variant names:

• chr8-96235770-A-T
• rs73698551
• ENST00000727543.1:n.125A>T

Variant summary

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

The NR_183272.1(UQCRB-AS1):​n.131A>T 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 0.0167 in 646,774 control chromosomes in the GnomAD database, including 855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (619 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (236 hom.)
• Consequence: UQCRB-AS1 NR_183272.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.155
• 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=-0.8).
• BP6: Variant 8-96235770-A-T is Benign according to our data. Variant chr8-96235770-A-T is described in ClinVar as Benign. ClinVar VariationId is 1253307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_183272.1. 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_183272.1		n.131A>T		non_coding_transcript_exon	Exon 1 of 3
	UQCRB-AS1	NR_183273.1		n.55+76A>T		intron	N/A
	UQCRB-AS1	NR_183274.1		n.269+209A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRB-AS1	ENST00000727543.1		n.125A>T		non_coding_transcript_exon	Exon 1 of 2
	UQCRB-AS1	ENST00000727544.1		n.133A>T		non_coding_transcript_exon	Exon 1 of 3
	UQCRB-AS1	ENST00000520575.2	TSL:2	n.271+209A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7522 AN: 152174 Hom.: 615 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.0339

GnomAD4 exome AF: 0.00654 AC: 3234 AN: 494482 Hom.: 236 AF XY: 0.00537 AC XY: 1424 AN XY: 265384

African (AFR) AF: 0.173 AC: 2445 AN: 14126

American (AMR) AF: 0.0104 AC: 294 AN: 28240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16462

East Asian (EAS) AF: 0.00 AC: 0 AN: 30832

South Asian (SAS) AF: 0.000382 AC: 21 AN: 55022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31266

Middle Eastern (MID) AF: 0.00790 AC: 17 AN: 2152

European-Non Finnish (NFE) AF: 0.000385 AC: 111 AN: 288632

Other (OTH) AF: 0.0125 AC: 346 AN: 27750

GnomAD4 genome AF: 0.0496 AC: 7555 AN: 152292 Hom.: 619 Cov.: 32 AF XY: 0.0474 AC XY: 3533 AN XY: 74470

African (AFR) AF: 0.173 AC: 7186 AN: 41524

American (AMR) AF: 0.0167 AC: 255 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68032

Other (OTH) AF: 0.0336 AC: 71 AN: 2116

Alfa AF: 0.0305 Hom.: 42

Bravo AF: 0.0561

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.80
CADD	Benign	2.6
DANN	Benign	0.79
PhyloP100		-0.15
PromoterAI		0.00070	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73698551; hg19: chr8-97247998;