rs7486178

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE3B	XM_011538961.2	c.3016-1069G>A		intron_variant	Intron 27 of 27		XP_011537263.1
UBE3B	XM_047429851.1	c.3016-1069G>A		intron_variant	Intron 27 of 27		XP_047285807.1
UBE3B	XM_047429852.1	c.3016-1069G>A		intron_variant	Intron 27 of 27		XP_047285808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;