Variant 11-118384947-TAAAAAAAAAAAAA-TAA 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+3_2412+13delAAAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,067,126 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

UBE4A
ENST00000252108.8 splice_region, 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 amr. gnomad4 allele frequency = 0.0024 (191/79504) while in subpopulation AMR AF= 0.00739 (51/6898). AF 95% confidence interval is 0.00578. There are 0 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UBE4A	NM_001204077.2 link	c.2412+13_2412+23delAAAAAAAAAAA	intron_variant	Intron 15 of 19	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4 link	c.2433+13_2433+23delAAAAAAAAAAA	intron_variant	Intron 15 of 19		NP_004779.2
LOC100131626	NR_046369.1 link	n.232-3398_232-3388delTTTTTTTTTTT	intron_variant	Intron 3 of 3
LOC100131626	NR_046370.1 link	n.232-3451_232-3441delTTTTTTTTTTT	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBE4A	ENST00000252108.8 link	c.2412+3_2412+13delAAAAAAAAAAA	splice_region_variant, intron_variant	Intron 15 of 19	1	NM_001204077.2	ENSP00000252108.4	Q14139-1
UBE4A	ENST00000431736.6 link	c.2433+3_2433+13delAAAAAAAAAAA	splice_region_variant, intron_variant	Intron 15 of 19	1		ENSP00000387362.2	Q14139-2
UBE4A	ENST00000545354.1 link	c.828+3_828+13delAAAAAAAAAAA	splice_region_variant, intron_variant	Intron 6 of 10	2		ENSP00000438918.1	B7Z7P0

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

191

AN:

79514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00622

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000267

Gnomad OTH

AF:

0.00295

GnomAD4 exome

AF:

0.000146

AC:

144

AN:

987622

Hom.:

AF XY:

0.000113

AC XY:

AN XY:

503546

show subpopulations

Gnomad4 AFR exome

AF:

0.00481

Gnomad4 AMR exome

AF:

0.000734

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000371

GnomAD4 genome

AF:

0.00240

AC:

191

AN:

79504

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

AN XY:

37782

show subpopulations

Gnomad4 AFR

AF:

0.00621

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000267

Gnomad4 OTH

AF:

0.00291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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