rs778480

Positions:

• chr3-23457001-G-A
• chr3-23457001-G-C
• chr3-23457001-G-T

Variant summary

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

The NM_152653.4(UBE2E2):​c.228-42607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,116 control chromosomes in the GnomAD database, including 36,229 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 0.67 (36229 hom., cov: 32)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2E2	NM_152653.4	c.228-42607G>A		intron_variant		ENST00000396703.6	NP_689866.1
UBE2E2	NM_001370225.1	c.228-42607G>A		intron_variant			NP_001357154.1
UBE2E2	NM_001370226.1	c.228-42607G>A		intron_variant			NP_001357155.1
UBE2E2	XM_047448843.1	c.228-42607G>A		intron_variant			XP_047304799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2E2	ENST00000396703.6	c.228-42607G>A		intron_variant		1	NM_152653.4	ENSP00000379931	P1
UBE2E2	ENST00000335798.8	c.228-75553G>A		intron_variant, NMD_transcript_variant		1		ENSP00000338340
UBE2E2	ENST00000425792.5	c.228-42607G>A		intron_variant		2		ENSP00000401053	P1
UBE2E2	ENST00000452894.5	c.300-42607G>A		intron_variant		3		ENSP00000392800

Frequencies

GnomAD3 genomes AF: 0.671 AC: 102011 AN: 151998 Hom.: 36180 Cov.: 32

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.671 AC: 102112 AN: 152116 Hom.: 36229 Cov.: 32 AF XY: 0.669 AC XY: 49718 AN XY: 74354

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.649

Alfa AF: 0.635 Hom.: 4669

Bravo AF: 0.672

Asia WGS AF: 0.669 AC: 2327 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	0.85
DANN	Benign	0.26

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: rs778480; hg19: chr3-23498492;