Genetic Variant UBE4B:c.435+11G>A (chr1-10101206-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2638194.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 418 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105562.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBE4B	NM_001105562.3	MANE Select	c.435+11G>A	intron	N/A	NP_001099032.1	O95155-1
UBE4B	NM_001410744.1		c.435+11G>A	intron	N/A	NP_001397673.1	O95155-4
UBE4B	NM_006048.5		c.435+11G>A	intron	N/A	NP_006039.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UBE4B	ENST00000343090.11	TSL:1 MANE Select	c.435+11G>A	intron	N/A	ENSP00000343001.6	O95155-1
UBE4B	ENST00000253251.12	TSL:1	c.435+11G>A	intron	N/A	ENSP00000253251.8	O95155-2
UBE4B	ENST00000672724.1		c.435+11G>A	intron	N/A	ENSP00000500453.1	O95155-4

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

GnomAD2 exomes

AF:

0.00262

AC:

659

AN:

251286

AF XY:

0.00267

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 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

African (AFR)

AF:

0.000329

AC:

AN:

33454

American (AMR)

AF:

0.00112

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000345

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39676

South Asian (SAS)

AF:

0.00123

AC:

106

AN:

86228

European-Finnish (FIN)

AF:

0.00858

AC:

458

AN:

53406

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00235

AC:

2609

AN:

1111040

Other (OTH)

AF:

0.00217

AC:

131

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

155

310

464

619

774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00274

AC:

418

AN:

152320

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41578

American (AMR)

AF:

0.00222

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00952

AC:

101

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00366

AC:

249

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00184

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over