XM_011538961.2:c.3016-1069G>A

Variant names:

• chr12-109542461-G-A
• rs7486178
• XM_011538961.2:c.3016-1069G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011538961.2(UBE3B):​c.3016-1069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,006 control chromosomes in the GnomAD database, including 12,841 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12841 hom., cov: 32)
• Consequence: UBE3B XM_011538961.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 8 publications found

Genes affected

UBE3B (HGNC:13478): (ubiquitin protein ligase E3B) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes, and E3 ubiquitin-protein ligases. This gene encodes a member of the E3 ubiquitin-conjugating enzyme family which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and transfers the ubiquitin to the targeted substrates. A HECT (homology to E6-AP C-terminus) domain in the C-terminus of the longer isoform of this protein is the catalytic site of ubiquitin transfer and forms a complex with E2 conjugases. Shorter isoforms of this protein which lack the C-terminal HECT domain are therefore unlikely to bind E2 enzymes. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2012]

UBE3B Gene-Disease associations (from GenCC):

• oculocerebrofacial syndrome, Kaufman type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60587 AN: 151888 Hom.: 12798 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.399 AC: 60685 AN: 152006 Hom.: 12841 Cov.: 32 AF XY: 0.395 AC XY: 29324 AN XY: 74306

African (AFR) AF: 0.541 AC: 22417 AN: 41452

American (AMR) AF: 0.347 AC: 5306 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1184 AN: 3470

East Asian (EAS) AF: 0.158 AC: 815 AN: 5160

South Asian (SAS) AF: 0.259 AC: 1246 AN: 4812

European-Finnish (FIN) AF: 0.365 AC: 3856 AN: 10558

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24556 AN: 67968

Other (OTH) AF: 0.407 AC: 859 AN: 2108

Alfa AF: 0.371 Hom.: 8683

Bravo AF: 0.406

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.1
DANN	Benign	0.92
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs7486178; hg19: chr12-109980266;