1-10101206-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001105562.3(UBE4B):c.435+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,613,076 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (11 hom.)
• Consequence: UBE4B NM_001105562.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-10101206-G-A is Benign according to our data. Variant chr1-10101206-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 418 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE4B	NM_001105562.3	c.435+11G>A		intron_variant		ENST00000343090.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE4B	ENST00000343090.11	c.435+11G>A		intron_variant		1	NM_001105562.3
UBE4B	ENST00000253251.12	c.435+11G>A		intron_variant		1		P1
UBE4B	ENST00000672724.1	c.435+11G>A		intron_variant
UBE4B	ENST00000462658.1	n.335+11G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 418 AN: 152202 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00262 AC: 659 AN: 251286 Hom.: 5 AF XY: 0.00267 AC XY: 363 AN XY: 135834

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00141

Gnomad FIN exome AF: 0.00975

Gnomad NFE exome AF: 0.00296

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00232 AC: 3383 AN: 1460756 Hom.: 11 Cov.: 29 AF XY: 0.00233 AC XY: 1693 AN XY: 726764

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.000345

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.00858

Gnomad4 NFE exome AF: 0.00235

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.00274 AC: 418 AN: 152320 Hom.: 2 Cov.: 32 AF XY: 0.00317 AC XY: 236 AN XY: 74490

Gnomad4 AFR AF: 0.000625

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00952

Gnomad4 NFE AF: 0.00366

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00162 Hom.: 0

Bravo AF: 0.00184

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

UBE4B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	15
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs41280790; hg19: chr1-10161264;