rs2241206

Variant names:

• chr12-109531043-T-C
• rs2241206
• NM_130466.4:c.2922+385T>C

Variant summary

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

The NM_130466.4(UBE3B):​c.2922+385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,224 control chromosomes in the GnomAD database, including 1,471 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 0.13 (1471 hom., cov: 32)
• Consequence: UBE3B NM_130466.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE3B	NM_130466.4	c.2922+385T>C		intron_variant	Intron 26 of 27	ENST00000342494.8	NP_569733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE3B	ENST00000342494.8	c.2922+385T>C		intron_variant	Intron 26 of 27	1	NM_130466.4	ENSP00000340596.3
UBE3B	ENST00000449510.6	n.*903+385T>C		intron_variant	Intron 27 of 28	5		ENSP00000395802.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19043 AN: 152106 Hom.: 1475 Cov.: 32

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.125 AC: 19041 AN: 152224 Hom.: 1471 Cov.: 32 AF XY: 0.121 AC XY: 9021 AN XY: 74424

African (AFR) AF: 0.0351 AC: 1458 AN: 41546

American (AMR) AF: 0.139 AC: 2120 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3470

East Asian (EAS) AF: 0.138 AC: 712 AN: 5170

South Asian (SAS) AF: 0.130 AC: 625 AN: 4824

European-Finnish (FIN) AF: 0.0991 AC: 1052 AN: 10618

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11855 AN: 67994

Other (OTH) AF: 0.145 AC: 307 AN: 2112

Alfa AF: 0.163 Hom.: 1179

Bravo AF: 0.127

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.82
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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: rs2241206; hg19: chr12-109968848; COSMIC: COSV61077309; COSMIC: COSV61077309;