11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAA

Variant names:

• chr11-118384947-T-TAAA
• rs370025001
• NM_001204077.2:c.2412+21_2412+23dupAAA

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+3insAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,066,970 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 0.000063 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00013 (0 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 = 0.0000629 (5/79504) while in subpopulation AFR AF= 0.000183 (4/21850). AF 95% confidence interval is 0.0000616. There are 0 homozygotes in gnomad4. There are 3 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+21_2412+23dupAAA		intron_variant	Intron 15 of 19	ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4	c.2433+21_2433+23dupAAA		intron_variant	Intron 15 of 19		NP_004779.2
LOC100131626	NR_046369.1	n.232-3390_232-3388dupTTT		intron_variant	Intron 3 of 3
LOC100131626	NR_046370.1	n.232-3443_232-3441dupTTT		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+3insAAA		splice_region_variant, intron_variant	Intron 15 of 19	1	NM_001204077.2	ENSP00000252108.4
UBE4A	ENST00000431736.6	c.2433+2_2433+3insAAA		splice_region_variant, intron_variant	Intron 15 of 19	1		ENSP00000387362.2
UBE4A	ENST00000545354.1	c.828+2_828+3insAAA		splice_region_variant, intron_variant	Intron 6 of 10	2		ENSP00000438918.1

Frequencies

GnomAD3 genomes AF: 0.0000629 AC: 5 AN: 79504 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000183

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000267

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 127 AN: 987466 Hom.: 0 Cov.: 0 AF XY: 0.000131 AC XY: 66 AN XY: 503464

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.0000699

Gnomad4 ASJ exome AF: 0.0000528

Gnomad4 EAS exome AF: 0.0000287

Gnomad4 SAS exome AF: 0.000189

Gnomad4 FIN exome AF: 0.000174

Gnomad4 NFE exome AF: 0.000130

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.0000629 AC: 5 AN: 79504 Hom.: 0 Cov.: 29 AF XY: 0.0000794 AC XY: 3 AN XY: 37760

Gnomad4 AFR AF: 0.000183

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

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;