chr3-23422323-A-G

Variant names:

• chr3-23422323-A-G
• rs1692617
• NM_152653.4:c.228-77285A>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.228-77285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,864 control chromosomes in the GnomAD database, including 29,640 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 0.62 (29640 hom., cov: 30)
• Consequence: UBE2E2 NM_152653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2E2	NM_152653.4	c.228-77285A>G		intron_variant	Intron 3 of 5	ENST00000396703.6	NP_689866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2E2	ENST00000396703.6	c.228-77285A>G		intron_variant	Intron 3 of 5	1	NM_152653.4	ENSP00000379931.1
UBE2E2	ENST00000335798.8	n.228-110231A>G		intron_variant	Intron 3 of 4	1		ENSP00000338340.4
UBE2E2	ENST00000425792.5	c.228-77285A>G		intron_variant	Intron 3 of 5	2		ENSP00000401053.1
UBE2E2	ENST00000452894.5	c.300-77285A>G		intron_variant	Intron 4 of 5	3		ENSP00000392800.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93684 AN: 151746 Hom.: 29601 Cov.: 30

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.617 AC: 93771 AN: 151864 Hom.: 29640 Cov.: 30 AF XY: 0.616 AC XY: 45695 AN XY: 74200

African (AFR) AF: 0.740 AC: 30657 AN: 41408

American (AMR) AF: 0.465 AC: 7103 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2083 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3460 AN: 5158

South Asian (SAS) AF: 0.627 AC: 3018 AN: 4812

European-Finnish (FIN) AF: 0.641 AC: 6747 AN: 10524

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38888 AN: 67910

Other (OTH) AF: 0.608 AC: 1283 AN: 2110

Alfa AF: 0.588 Hom.: 13580

Bravo AF: 0.608

Asia WGS AF: 0.636 AC: 2212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		-0.21
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: rs1692617; hg19: chr3-23463814;