chr11-118384947-TAAAAAAA-T

Position:

• chr11-118384947-TAAAAAAA-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+17_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 0.000162 in 1,066,638 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 0.000050 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00017 (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 eas. gnomad4 allele frequency = 0.0000503 (4/79514) while in subpopulation EAS AF= 0.00102 (3/2948). AF 95% confidence interval is 0.000277. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.2412+17_2412+23del		splice_donor_5th_base_variant, intron_variant		ENST00000252108.8	NP_001191006.1
LOC100131626	NR_046370.1	n.232-3447_232-3441del		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2433+17_2433+23del		splice_donor_5th_base_variant, intron_variant			NP_004779.2
LOC100131626	NR_046369.1	n.232-3394_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+17_2412+23del		splice_donor_5th_base_variant, intron_variant		1	NM_001204077.2	ENSP00000252108	P1
UBE4A	ENST00000431736.6	c.2433+17_2433+23del		splice_donor_5th_base_variant, intron_variant		1		ENSP00000387362
UBE4A	ENST00000545354.1	c.828+17_828+23del		splice_donor_5th_base_variant, intron_variant		2		ENSP00000438918

Frequencies

GnomAD3 genomes AF: 0.0000503 AC: 4 AN: 79514 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: 0.00102

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: 0.000171 AC: 169 AN: 987124 Hom.: 0 AF XY: 0.000171 AC XY: 86 AN XY: 503288

Gnomad4 AFR exome AF: 0.000225

Gnomad4 AMR exome AF: 0.000140

Gnomad4 ASJ exome AF: 0.000158

Gnomad4 EAS exome AF: 0.000173

Gnomad4 SAS exome AF: 0.000126

Gnomad4 FIN exome AF: 0.000116

Gnomad4 NFE exome AF: 0.000179

Gnomad4 OTH exome AF: 0.000162

GnomAD4 genome AF: 0.0000503 AC: 4 AN: 79514 Hom.: 0 Cov.: 29 AF XY: 0.0000530 AC XY: 2 AN XY: 37762

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00102

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;