chr11-118384947-TAAAAA-T

Position:

• chr11-118384947-TAAAAA-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001204077.2(UBE4A):​c.2412+19_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 0.00416 in 1,056,924 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 0.000038 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0045 (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 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 afr. gnomad4_exome allele frequency = 0.00449 (4390/977416) while in subpopulation AFR AF= 0.00638 (140/21928). AF 95% confidence interval is 0.00552. There are 0 homozygotes in gnomad4_exome. There are 2233 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.2412+19_2412+23del		splice_donor_5th_base_variant, intron_variant		ENST00000252108.8	NP_001191006.1
LOC100131626	NR_046370.1	n.232-3445_232-3441del		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2433+19_2433+23del		splice_donor_5th_base_variant, intron_variant			NP_004779.2
LOC100131626	NR_046369.1	n.232-3392_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+19_2412+23del		splice_donor_5th_base_variant, intron_variant		1	NM_001204077.2	ENSP00000252108	P1
UBE4A	ENST00000431736.6	c.2433+19_2433+23del		splice_donor_5th_base_variant, intron_variant		1		ENSP00000387362
UBE4A	ENST00000545354.1	c.828+19_828+23del		splice_donor_5th_base_variant, intron_variant		2		ENSP00000438918

Frequencies

GnomAD3 genomes AF: 0.0000377 AC: 3 AN: 79508 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000478

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000267

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00485 AC: 406 AN: 83660 Hom.: 0 AF XY: 0.00482 AC XY: 218 AN XY: 45246

Gnomad AFR exome AF: 0.00457

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.00726

Gnomad EAS exome AF: 0.00552

Gnomad SAS exome AF: 0.00595

Gnomad FIN exome AF: 0.00596

Gnomad NFE exome AF: 0.00430

Gnomad OTH exome AF: 0.00513

GnomAD4 exome AF: 0.00449 AC: 4390 AN: 977416 Hom.: 0 AF XY: 0.00448 AC XY: 2233 AN XY: 498186

Gnomad4 AFR exome AF: 0.00638

Gnomad4 AMR exome AF: 0.00450

Gnomad4 ASJ exome AF: 0.00590

Gnomad4 EAS exome AF: 0.00380

Gnomad4 SAS exome AF: 0.00379

Gnomad4 FIN exome AF: 0.00430

Gnomad4 NFE exome AF: 0.00451

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0000377 AC: 3 AN: 79508 Hom.: 0 Cov.: 29 AF XY: 0.0000265 AC XY: 1 AN XY: 37758

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000478

Gnomad4 NFE AF: 0.0000267

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;