rs502514

Positions:

• chr11-118371280-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204077.2(UBE4A):​c.409-234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,038 control chromosomes in the GnomAD database, including 4,998 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4998 hom., cov: 31)
• Consequence: UBE4A NM_001204077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4A	NM_001204077.2	c.409-234T>C		intron_variant		ENST00000252108.8	NP_001191006.1
UBE4A	NM_004788.4	c.409-234T>C		intron_variant			NP_004779.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE4A	ENST00000252108.8	c.409-234T>C		intron_variant		1	NM_001204077.2	ENSP00000252108.4
UBE4A	ENST00000431736.6	c.409-234T>C		intron_variant		1		ENSP00000387362.2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35194 AN: 151920 Hom.: 5003 Cov.: 31

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.231 AC: 35171 AN: 152038 Hom.: 4998 Cov.: 31 AF XY: 0.231 AC XY: 17173 AN XY: 74294

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.243

Alfa AF: 0.294 Hom.: 3538

Bravo AF: 0.218

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs502514; hg19: chr11-118241995;