Variant 1-10101105-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001105562.3(UBE4B):c.348-3A>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0036 in 1,613,930 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 59 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 64 hom. )

Consequence

UBE4B
NM_001105562.3 splice_region, intron

Scores

Splicing: ADA: 0.001032

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.02

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 1-10101105-A-C is Benign according to our data. Variant chr1-10101105-A-C is described in ClinVar as [Benign]. Clinvar id is 775508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4B	NM_001105562.3 link	c.348-3A>C		splice_region_variant, intron_variant		ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBE4B	ENST00000343090.11 link	c.348-3A>C	splice_region_variant, intron_variant		1	NM_001105562.3	ENSP00000343001.6	O95155-1
UBE4B	ENST00000253251.12 link	c.348-3A>C	splice_region_variant, intron_variant		1		ENSP00000253251.8	O95155-2
UBE4B	ENST00000672724.1 link	c.348-3A>C	splice_region_variant, intron_variant				ENSP00000500453.1	O95155-4
UBE4B	ENST00000462658.1 link	n.245A>C	non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2471

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0553

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00486

AC:

1221

AN:

251422

Hom.:

AF XY:

0.00395

AC XY:

537

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0589

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000897

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00228

AC:

3330

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1490

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0602

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000681

Gnomad4 OTH exome

AF:

0.00437

GnomAD4 genome

AF:

0.0162

AC:

2473

AN:

152350

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1196

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0552

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00828

Hom.:

Bravo

AF:

0.0183

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.16

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

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