rs370025001

chr11-118384947-TAAAAAAAAAAAAA-Tchr11-118384947-TAAAAAAAAAAAAA-TAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAchr11-118384947-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001204077.2(UBE4A):c.2412+11_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 0.000015 in 1,067,142 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: 0.000013 (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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE4A	NM_001204077.2	c.2412+11_2412+23del		splice_donor_5th_base_variant, intron_variant		ENST00000252108.8
LOC100131626	NR_046370.1	n.232-3453_232-3441del		intron_variant, non_coding_transcript_variant
UBE4A	NM_004788.4	c.2433+11_2433+23del		splice_donor_5th_base_variant, intron_variant
LOC100131626	NR_046369.1	n.232-3400_232-3388del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE4A	ENST00000252108.8	c.2412+11_2412+23del		splice_donor_5th_base_variant, intron_variant		1	NM_001204077.2	P1
UBE4A	ENST00000431736.6	c.2433+11_2433+23del		splice_donor_5th_base_variant, intron_variant		1
UBE4A	ENST00000545354.1	c.828+11_828+23del		splice_donor_5th_base_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000377 AC: 3 AN: 79516 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000915

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: 0.0000132 AC: 13 AN: 987626 Hom.: 0 AF XY: 0.0000199 AC XY: 10 AN XY: 503546

Gnomad4 AFR exome AF: 0.0000899

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000136

Gnomad4 OTH exome AF: 0.0000232

GnomAD4 genome AF: 0.0000377 AC: 3 AN: 79516 Hom.: 0 Cov.: 29 AF XY: 0.0000265 AC XY: 1 AN XY: 37764

Gnomad4 AFR AF: 0.0000915

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

Bravo AF: 0.00000756

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;