1-10130826-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001105562.3(UBE4B):c.1911+13A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,609,586 control chromosomes in the GnomAD database, including 134,203 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 0.47 (17539 hom., cov: 32)
  • Exomes 𝑓: 0.40 (116664 hom.)
• Consequence: UBE4B NM_001105562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

Genes affected

UBE4B (HGNC:12500): (ubiquitination factor E4B) 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: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes an additional conjugation factor, E4, which is involved in multiubiquitin chain assembly. This gene is also the strongest candidate in the neuroblastoma tumor suppressor genes. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE4B	NM_001105562.3	c.1911+13A>T		intron_variant		ENST00000343090.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE4B	ENST00000343090.11	c.1911+13A>T		intron_variant		1	NM_001105562.3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70648 AN: 151932 Hom.: 17509 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.441

GnomAD3 exomes AF: 0.420 AC: 105097 AN: 250144 Hom.: 22859 AF XY: 0.410 AC XY: 55418 AN XY: 135170

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.412

Gnomad SAS exome AF: 0.385

Gnomad FIN exome AF: 0.357

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.397 AC: 578047 AN: 1457536 Hom.: 116664 Cov.: 31 AF XY: 0.395 AC XY: 286240 AN XY: 725354

Gnomad4 AFR exome AF: 0.649

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.465 AC: 70727 AN: 152050 Hom.: 17539 Cov.: 32 AF XY: 0.462 AC XY: 34314 AN XY: 74316

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.444

Alfa AF: 0.415 Hom.: 2478

Bravo AF: 0.484

Asia WGS AF: 0.421 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	16
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295294; hg19: chr1-10190884; COSMIC: COSV53528852;