3-23531115-A-G

Variant names:

• chr3-23531115-A-G
• rs2173460
• NM_152653.4:c.361-1439A>G

Variant summary

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

The NM_152653.4(UBE2E2):​c.361-1439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,002 control chromosomes in the GnomAD database, including 26,937 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 0.58 (26937 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 3 publications found

Genes affected

UBE2E2 (HGNC:12478): (ubiquitin conjugating enzyme E2 E2) Enables ISG15 transferase activity and ubiquitin conjugating enzyme activity. Involved in protein modification by small protein conjugation. Acts upstream of or within cellular response to DNA damage stimulus and positive regulation of G1/S transition of mitotic cell cycle. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2E2	NM_152653.4	c.361-1439A>G		intron_variant	Intron 4 of 5	ENST00000396703.6	NP_689866.1
UBE2E2	NM_001370225.1	c.361-1439A>G		intron_variant	Intron 4 of 5		NP_001357154.1
UBE2E2	NM_001370226.1	c.361-1439A>G		intron_variant	Intron 4 of 5		NP_001357155.1
UBE2E2	XM_047448843.1	c.361-1439A>G		intron_variant	Intron 4 of 5		XP_047304799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2E2	ENST00000396703.6	c.361-1439A>G		intron_variant	Intron 4 of 5	1	NM_152653.4	ENSP00000379931.1
UBE2E2	ENST00000335798.8	n.228-1439A>G		intron_variant	Intron 3 of 4	1		ENSP00000338340.4
UBE2E2	ENST00000425792.5	c.361-1439A>G		intron_variant	Intron 4 of 5	2		ENSP00000401053.1
UBE2E2	ENST00000452894.5	c.433-1439A>G		intron_variant	Intron 5 of 5	3		ENSP00000392800.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87779 AN: 151884 Hom.: 26908 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.578 AC: 87858 AN: 152002 Hom.: 26937 Cov.: 32 AF XY: 0.576 AC XY: 42789 AN XY: 74298

African (AFR) AF: 0.789 AC: 32702 AN: 41462

American (AMR) AF: 0.437 AC: 6672 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3810 AN: 5170

South Asian (SAS) AF: 0.621 AC: 2986 AN: 4812

European-Finnish (FIN) AF: 0.486 AC: 5119 AN: 10536

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32994 AN: 67970

Other (OTH) AF: 0.564 AC: 1190 AN: 2110

Alfa AF: 0.393 Hom.: 1083

Bravo AF: 0.583

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.4
DANN	Benign	0.47
PhyloP100		0.14
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: rs2173460; hg19: chr3-23572606;