11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Position:

• chr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001204077.2(UBE4A):​c.2412+23dup variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,062,816 control chromosomes in the GnomAD database, including 38 homozygotes. 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 0.036 (37 hom., cov: 29)
  • Exomes 𝑓: 0.014 (1 hom.)
• Consequence: UBE4A NM_001204077.2 splice_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.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0364 (2891/79388) while in subpopulation NFE AF= 0.0381 (1424/37362). AF 95% confidence interval is 0.0365. There are 37 homozygotes in gnomad4. There are 1362 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE4A	NM_001204077.2	c.2412+23dup		splice_region_variant, intron_variant		ENST00000252108.8
LOC100131626	NR_046370.1	n.232-3441_232-3440insT		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2433+23dup		splice_region_variant, intron_variant
LOC100131626	NR_046369.1	n.232-3388_232-3387insT		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 2901 AN: 79398 Hom.: 38 Cov.: 29

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.0112

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0105

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0373

GnomAD3 exomes AF: 0.0144 AC: 1204 AN: 83660 Hom.: 0 AF XY: 0.0134 AC XY: 608 AN XY: 45246

Gnomad AFR exome AF: 0.0165

Gnomad AMR exome AF: 0.0173

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.0200

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.00757

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.0196

GnomAD4 exome AF: 0.0144 AC: 14129 AN: 983428 Hom.: 1 Cov.: 0 AF XY: 0.0143 AC XY: 7164 AN XY: 501262

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.0137

Gnomad4 EAS exome AF: 0.00762

Gnomad4 SAS exome AF: 0.0179

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.0146

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0364 AC: 2891 AN: 79388 Hom.: 37 Cov.: 29 AF XY: 0.0361 AC XY: 1362 AN XY: 37724

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0368

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;