11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAA

Position:

• chr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAA

Variant summary

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

The NM_001204077.2(UBE4A):​c.2412+22_2412+23del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,007,182 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 0.0020 (0 hom., cov: 29)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: UBE4A NM_001204077.2 splice_donor_region, 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 (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.2412+22_2412+23del		splice_donor_region_variant, intron_variant		ENST00000252108.8	NP_001191006.1
LOC100131626	NR_046370.1	n.232-3442_232-3441del		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2433+22_2433+23del		splice_donor_region_variant, intron_variant			NP_004779.2
LOC100131626	NR_046369.1	n.232-3389_232-3388del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE4A	ENST00000252108.8	c.2412+22_2412+23del		splice_donor_region_variant, intron_variant		1	NM_001204077.2	ENSP00000252108	P1
UBE4A	ENST00000431736.6	c.2433+22_2433+23del		splice_donor_region_variant, intron_variant		1		ENSP00000387362
UBE4A	ENST00000545354.1	c.828+22_828+23del		splice_donor_region_variant, intron_variant		2		ENSP00000438918

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 162 AN: 79398 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00188

Gnomad ASJ AF: 0.000501

Gnomad EAS AF: 0.000339

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00152

Gnomad OTH AF: 0.000982

GnomAD3 exomes AF: 0.191 AC: 15984 AN: 83660 Hom.: 1 AF XY: 0.191 AC XY: 8654 AN XY: 45246

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.151 AC: 139794 AN: 927796 Hom.: 0 AF XY: 0.152 AC XY: 71360 AN XY: 470852

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.00204 AC: 162 AN: 79386 Hom.: 0 Cov.: 29 AF XY: 0.00228 AC XY: 86 AN XY: 37712

Gnomad4 AFR AF: 0.00192

Gnomad4 AMR AF: 0.00188

Gnomad4 ASJ AF: 0.000501

Gnomad4 EAS AF: 0.000341

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0113

Gnomad4 NFE AF: 0.00152

Gnomad4 OTH AF: 0.000969

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;