chr11-57553849-T-C

Variant names:

• chr11-57553849-T-C
• rs2729371
• NM_004223.5:c.310+588A>G

Variant summary

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

The NM_004223.5(UBE2L6):​c.310+588A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,192 control chromosomes in the GnomAD database, including 53,943 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 0.84 (53943 hom., cov: 31)
• Consequence: UBE2L6 NM_004223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 25 publications found

Genes affected

UBE2L6 (HGNC:12490): (ubiquitin conjugating enzyme E2 L6) 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 highly similar in primary structure to the enzyme encoded by the UBE2L3 gene. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2L6	NM_004223.5	c.310+588A>G		intron_variant	Intron 3 of 3	ENST00000287156.9	NP_004214.1
UBE2L6	NM_198183.3	c.112+588A>G		intron_variant	Intron 3 of 3		NP_937826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2L6	ENST00000287156.9	c.310+588A>G		intron_variant	Intron 3 of 3	1	NM_004223.5	ENSP00000287156.4

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127475 AN: 152074 Hom.: 53891 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.838 AC: 127582 AN: 152192 Hom.: 53943 Cov.: 31 AF XY: 0.841 AC XY: 62564 AN XY: 74400

African (AFR) AF: 0.938 AC: 38995 AN: 41556

American (AMR) AF: 0.811 AC: 12403 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2930 AN: 3468

East Asian (EAS) AF: 0.930 AC: 4813 AN: 5174

South Asian (SAS) AF: 0.799 AC: 3856 AN: 4826

European-Finnish (FIN) AF: 0.822 AC: 8698 AN: 10582

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.782 AC: 53189 AN: 67982

Other (OTH) AF: 0.817 AC: 1724 AN: 2110

Alfa AF: 0.810 Hom.: 10695

Bravo AF: 0.842

Asia WGS AF: 0.858 AC: 2983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.54
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2729371; hg19: chr11-57321322;