rs1949453

Variant names:

• chr2-181046047-T-A
• rs1949453
• NM_006357.4:c.246-11646T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-181046047-T-A
• chr2-181046047-T-C
• chr2-181046047-T-G

Variant summary

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

The NM_006357.4(UBE2E3):​c.246-11646T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,018 control chromosomes in the GnomAD database, including 23,321 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 0.54 (23321 hom., cov: 32)
• Consequence: UBE2E3 NM_006357.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 2 publications found

Genes affected

UBE2E3 (HGNC:12479): (ubiquitin conjugating enzyme E2 E3) 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, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein shares 100% sequence identity with the mouse and rat counterparts, which indicates that this enzyme is highly conserved in eukaryotes. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2E3	NM_006357.4	c.246-11646T>A		intron_variant	Intron 3 of 5	ENST00000410062.9	NP_006348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2E3	ENST00000410062.9	c.246-11646T>A		intron_variant	Intron 3 of 5	1	NM_006357.4	ENSP00000386788.3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82192 AN: 151898 Hom.: 23265 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.541 AC: 82308 AN: 152018 Hom.: 23321 Cov.: 32 AF XY: 0.549 AC XY: 40746 AN XY: 74286

African (AFR) AF: 0.664 AC: 27515 AN: 41466

American (AMR) AF: 0.584 AC: 8912 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3470

East Asian (EAS) AF: 0.796 AC: 4116 AN: 5168

South Asian (SAS) AF: 0.646 AC: 3118 AN: 4824

European-Finnish (FIN) AF: 0.509 AC: 5378 AN: 10558

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30233 AN: 67960

Other (OTH) AF: 0.513 AC: 1085 AN: 2114

Alfa AF: 0.376 Hom.: 1077

Bravo AF: 0.551

Asia WGS AF: 0.753 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.62
PhyloP100		0.36
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: rs1949453; hg19: chr2-181910774;