Variant 11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The ENST00000252108.8(UBE4A):c.2412+20_2412+23del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,035,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000038 ( 0 hom., cov: 29)

Exomes 𝑓: 0.019 ( 0 hom. )

Consequence

UBE4A
ENST00000252108.8 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

UBE4A (HGNC:12499): (ubiquitination factor E4A) This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

UBE4A links:

LOC100131626 (HGNC:):

LOC100131626 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0185 (17712/956032) while in subpopulation AFR AF= 0.0239 (512/21378). AF 95% confidence interval is 0.0222. There are 0 homozygotes in gnomad4_exome. There are 9006 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
UBE4A	NM_001204077.2 linkuse as main transcript	c.2412+20_2412+23del	splice_donor_5th_base_variant, intron_variant	ENST00000252108.8	NP_001191006.1
LOC100131626	NR_046370.1 linkuse as main transcript	n.232-3444_232-3441del	intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4 linkuse as main transcript	c.2433+20_2433+23del	splice_donor_5th_base_variant, intron_variant		NP_004779.2
LOC100131626	NR_046369.1 linkuse as main transcript	n.232-3391_232-3388del	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
UBE4A	ENST00000252108.8 linkuse as main transcript	c.2412+20_2412+23del	splice_donor_5th_base_variant, intron_variant	1	NM_001204077.2	ENSP00000252108	P1	Q14139-1
UBE4A	ENST00000431736.6 linkuse as main transcript	c.2433+20_2433+23del	splice_donor_5th_base_variant, intron_variant	1		ENSP00000387362		Q14139-2
UBE4A	ENST00000545354.1 linkuse as main transcript	c.828+20_828+23del	splice_donor_5th_base_variant, intron_variant	2		ENSP00000438918

Frequencies

GnomAD3 genomes

AF:

0.0000377

AC:

AN:

79482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000717

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0309

AC:

2582

AN:

83660

Hom.:

AF XY:

0.0316

AC XY:

1430

AN XY:

45246

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.0234

Gnomad EAS exome

AF:

0.0287

Gnomad SAS exome

AF:

0.0283

Gnomad FIN exome

AF:

0.0408

Gnomad NFE exome

AF:

0.0323

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0185

AC:

17712

AN:

956032

Hom.:

AF XY:

0.0185

AC XY:

9006

AN XY:

486470

show subpopulations

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.0197

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0204

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.0205

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0000377

AC:

AN:

79472

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

37764

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000717

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over