rs140489

Variant names:

• chr22-21567005-G-A
• rs140489
• NM_001256355.1:c.201+17355G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-21567005-G-A
• chr22-21567005-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256355.1(UBE2L3):​c.201+17355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,878 control chromosomes in the GnomAD database, including 8,393 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 0.31 (8393 hom., cov: 31)
• Consequence: UBE2L3 NM_001256355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 19 publications found

Genes affected

UBE2L3 (HGNC:12488): (ubiquitin conjugating enzyme E2 L3) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is demonstrated to participate in the ubiquitination of p53, c-Fos, and the NF-kB precursor p105 in vitro. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

UBE2L3 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2L3	NM_001256355.1	c.201+17355G>A		intron_variant	Intron 1 of 3		NP_001243284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000458578.6	c.201+17355G>A		intron_variant	Intron 1 of 3	2		ENSP00000400906.2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46870 AN: 151760 Hom.: 8353 Cov.: 31

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.309 AC: 46964 AN: 151878 Hom.: 8393 Cov.: 31 AF XY: 0.320 AC XY: 23782 AN XY: 74216

African (AFR) AF: 0.443 AC: 18321 AN: 41390

American (AMR) AF: 0.356 AC: 5433 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3464

East Asian (EAS) AF: 0.514 AC: 2657 AN: 5166

South Asian (SAS) AF: 0.395 AC: 1901 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3646 AN: 10526

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13372 AN: 67968

Other (OTH) AF: 0.292 AC: 613 AN: 2102

Alfa AF: 0.252 Hom.: 890

Bravo AF: 0.317

Asia WGS AF: 0.502 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.26
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs140489; hg19: chr22-21921294;