11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAA

Variant names:

• chr11-118384947-T-TAA
• rs370025001
• NM_001204077.2:c.2412+22_2412+23dupAA

Variant summary

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

The ENST00000252108.8(UBE4A):​c.2412+2_2412+3insAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,066,192 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00099 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00088 (1 hom.)
• Consequence: UBE4A ENST00000252108.8 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 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 allele frequency = 0.000994 (79/79466) while in subpopulation AFR AF= 0.00228 (50/21894). AF 95% confidence interval is 0.00178. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.2412+22_2412+23dupAA		intron_variant	Intron 15 of 19	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4	c.2433+22_2433+23dupAA		intron_variant	Intron 15 of 19		NP_004779.2
LOC100131626	NR_046369.1	n.232-3389_232-3388dupTT		intron_variant	Intron 3 of 3
LOC100131626	NR_046370.1	n.232-3442_232-3441dupTT		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE4A	ENST00000252108.8	c.2412+2_2412+3insAA		splice_region_variant, intron_variant	Intron 15 of 19	1	NM_001204077.2	ENSP00000252108.4
UBE4A	ENST00000431736.6	c.2433+2_2433+3insAA		splice_region_variant, intron_variant	Intron 15 of 19	1		ENSP00000387362.2
UBE4A	ENST00000545354.1	c.828+2_828+3insAA		splice_region_variant, intron_variant	Intron 6 of 10	2		ENSP00000438918.1

Frequencies

GnomAD3 genomes AF: 0.000994 AC: 79 AN: 79476 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00130

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000339

Gnomad SAS AF: 0.00155

Gnomad FIN AF: 0.000477

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000347

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000877 AC: 865 AN: 986726 Hom.: 1 Cov.: 0 AF XY: 0.000889 AC XY: 447 AN XY: 503060

Gnomad4 AFR exome AF: 0.00130

Gnomad4 AMR exome AF: 0.000735

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.000575

Gnomad4 SAS exome AF: 0.00151

Gnomad4 FIN exome AF: 0.000464

Gnomad4 NFE exome AF: 0.000845

Gnomad4 OTH exome AF: 0.000812

GnomAD4 genome AF: 0.000994 AC: 79 AN: 79466 Hom.: 0 Cov.: 29 AF XY: 0.00101 AC XY: 38 AN XY: 37768

Gnomad4 AFR AF: 0.00228

Gnomad4 AMR AF: 0.00130

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000341

Gnomad4 SAS AF: 0.00157

Gnomad4 FIN AF: 0.000477

Gnomad4 NFE AF: 0.000348

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;