11-118384947-TAAA-T

Position:

• chr11-118384947-TAAA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001204077.2(UBE4A):​c.2412+21_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 0.0565 in 999,732 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 0.00034 (0 hom., cov: 29)
  • Exomes 𝑓: 0.061 (0 hom.)
• Consequence: UBE4A NM_001204077.2 splice_donor_5th_base, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

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]

LOC100131626 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE4A	NM_001204077.2	c.2412+21_2412+23del		splice_donor_5th_base_variant, intron_variant		ENST00000252108.8
LOC100131626	NR_046370.1	n.232-3443_232-3441del		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2433+21_2433+23del		splice_donor_5th_base_variant, intron_variant
LOC100131626	NR_046369.1	n.232-3390_232-3388del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE4A	ENST00000252108.8	c.2412+21_2412+23del		splice_donor_5th_base_variant, intron_variant		1	NM_001204077.2	P1
UBE4A	ENST00000431736.6	c.2433+21_2433+23del		splice_donor_5th_base_variant, intron_variant		1
UBE4A	ENST00000545354.1	c.828+21_828+23del		splice_donor_5th_base_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000340 AC: 27 AN: 79454 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000435

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.116 AC: 9713 AN: 83660 Hom.: 0 AF XY: 0.116 AC XY: 5236 AN XY: 45246

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.0614 AC: 56500 AN: 920288 Hom.: 0 AF XY: 0.0619 AC XY: 28878 AN XY: 466892

Gnomad4 AFR exome AF: 0.0713

Gnomad4 AMR exome AF: 0.0730

Gnomad4 ASJ exome AF: 0.0725

Gnomad4 EAS exome AF: 0.0717

Gnomad4 SAS exome AF: 0.0598

Gnomad4 FIN exome AF: 0.0741

Gnomad4 NFE exome AF: 0.0592

Gnomad4 OTH exome AF: 0.0670

GnomAD4 genome AF: 0.000340 AC: 27 AN: 79444 Hom.: 0 Cov.: 29 AF XY: 0.000424 AC XY: 16 AN XY: 37742

Gnomad4 AFR AF: 0.000228

Gnomad4 AMR AF: 0.000435

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00192

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs370025001; hg19: chr11-118255662;