Variant 1-10101206-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.143

Variant links:

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]

UBE4B links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 418 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4B	NM_001105562.3 linkuse as main transcript	c.435+11G>A		intron_variant		ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
UBE4B	ENST00000343090.11 linkuse as main transcript	c.435+11G>A	intron_variant	1	NM_001105562.3	ENSP00000343001		O95155-1
UBE4B	ENST00000253251.12 linkuse as main transcript	c.435+11G>A	intron_variant	1		ENSP00000253251	P1	O95155-2
UBE4B	ENST00000672724.1 linkuse as main transcript	c.435+11G>A	intron_variant			ENSP00000500453		O95155-4
UBE4B	ENST00000462658.1 linkuse as main transcript	n.335+11G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

418

AN:

152202

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00267

AC XY:

363

AN XY:

135834

show subpopulations

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.:

Cov.:

AF XY:

0.00233

AC XY:

1693

AN XY:

726764

show subpopulations

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.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74490

show subpopulations

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.:

Bravo

AF:

0.00184

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over