11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAA

Position:

• chr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001204077.2(UBE4A):​c.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 0.192 in 1,056,106 control chromosomes in the GnomAD database, including 244 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (180 hom., cov: 29)
  • Exomes 𝑓: 0.20 (64 hom.)
• Consequence: UBE4A NM_001204077.2 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -16 ACMG points.

• BP6: Variant 11-118384947-TA-T is Benign according to our data. Variant chr11-118384947-TA-T is described in ClinVar as [Benign]. Clinvar id is 403581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.2412+23del		splice_donor_region_variant, intron_variant		ENST00000252108.8	NP_001191006.1
LOC100131626	NR_046370.1	n.232-3441del		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2433+23del		splice_donor_region_variant, intron_variant			NP_004779.2
LOC100131626	NR_046369.1	n.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+23del		splice_donor_region_variant, intron_variant		1	NM_001204077.2	ENSP00000252108	P1
UBE4A	ENST00000431736.6	c.2433+23del		splice_donor_region_variant, intron_variant		1		ENSP00000387362
UBE4A	ENST00000545354.1	c.828+23del		splice_donor_region_variant, intron_variant		2		ENSP00000438918

Frequencies

GnomAD3 genomes AF: 0.0895 AC: 7114 AN: 79474 Hom.: 178 Cov.: 29

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0520

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0846

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0866

GnomAD3 exomes AF: 0.135 AC: 11307 AN: 83660 Hom.: 6 AF XY: 0.132 AC XY: 5985 AN XY: 45246

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.201 AC: 195925 AN: 976640 Hom.: 64 Cov.: 0 AF XY: 0.197 AC XY: 98262 AN XY: 497596

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.0897 AC: 7125 AN: 79466 Hom.: 180 Cov.: 29 AF XY: 0.0893 AC XY: 3372 AN XY: 37758

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0614

Gnomad4 ASJ AF: 0.0520

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0883

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside ROI, Frequency -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Jun 11, 2015	- -

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;