rs1496653

Positions:

• chr3-23413299-A-G

Variant summary

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

The NM_152653.4(UBE2E2):​c.228-86309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,038 control chromosomes in the GnomAD database, including 5,303 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 0.25 (5303 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2E2	NM_152653.4	c.228-86309A>G		intron_variant		ENST00000396703.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2E2	ENST00000396703.6	c.228-86309A>G		intron_variant		1	NM_152653.4	P1
UBE2E2	ENST00000335798.8	c.228-119255A>G		intron_variant, NMD_transcript_variant		1
UBE2E2	ENST00000425792.5	c.228-86309A>G		intron_variant		2		P1
UBE2E2	ENST00000452894.5	c.300-86309A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38343 AN: 151920 Hom.: 5291 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.253 AC: 38390 AN: 152038 Hom.: 5303 Cov.: 32 AF XY: 0.256 AC XY: 19004 AN XY: 74286

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.228

Alfa AF: 0.204 Hom.: 6924

Bravo AF: 0.244

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.56

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: rs1496653; hg19: chr3-23454790;