chr20-50082386-G-A

Variant names:

• chr20-50082386-G-A
• rs8585
• ENST00000396059.7:n.721C>T

Variant summary

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

The ENST00000396059.7(UBE2V1):​n.721C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 192,996 control chromosomes in the GnomAD database, including 11,781 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 0.35 (10301 hom., cov: 31)
  • Exomes 𝑓: 0.25 (1480 hom.)
• Consequence: UBE2V1 ENST00000396059.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• Publications: 6 publications found

Genes affected

UBE2V1 (HGNC:12494): (ubiquitin conjugating enzyme E2 V1) Ubiquitin-conjugating E2 enzyme variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein encoded by this gene is located in the nucleus and can cause transcriptional activation of the human FOS proto-oncogene. It is thought to be involved in the control of differentiation by altering cell cycle behavior. Alternatively spliced transcript variants encoding multiple isoforms have been described for this gene, and multiple pseudogenes of this gene have been identified. Co-transcription of this gene and the neighboring upstream gene generates a rare transcript (Kua-UEV), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Apr 2012]

PEDS1-UBE2V1 (HGNC:33521): (PEDS1-UBE2V1 readthrough) The TMEM189-UEV mRNA is an infrequent but naturally occurring read-through transcript of the neighboring TMEM189 and UBE2V1 genes. Ubiquitin-conjugating E2 enzyme variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence similarity to other ubiquitin-conjugating enzymes but lack the conserved cysteine residue that is critical for the catalytic activity of E2s. The protein produced by this transcript has UEV1 B domains but the protein is localized to the cytoplasm rather than to the nucleus. The significance of this read-through mRNA and the function of its protein product has not yet been determined. [provided by RefSeq, Oct 2010]

ENSG00000306197 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2V1	NM_001032288.3	c.*382C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000371674.8	NP_001027459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2V1	ENST00000371674.8	c.*382C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_001032288.3	ENSP00000360739.4
PEDS1-UBE2V1	ENST00000341698.2	c.*382C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000344166.2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52639 AN: 151772 Hom.: 10277 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.250 AC: 10261 AN: 41106 Hom.: 1480 Cov.: 2 AF XY: 0.259 AC XY: 5877 AN XY: 22698

African (AFR) AF: 0.490 AC: 243 AN: 496

American (AMR) AF: 0.253 AC: 748 AN: 2956

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 192 AN: 814

East Asian (EAS) AF: 0.254 AC: 399 AN: 1568

South Asian (SAS) AF: 0.324 AC: 2070 AN: 6390

European-Finnish (FIN) AF: 0.233 AC: 462 AN: 1980

Middle Eastern (MID) AF: 0.346 AC: 36 AN: 104

European-Non Finnish (NFE) AF: 0.225 AC: 5606 AN: 24964

Other (OTH) AF: 0.275 AC: 505 AN: 1834

GnomAD4 genome AF: 0.347 AC: 52707 AN: 151890 Hom.: 10301 Cov.: 31 AF XY: 0.345 AC XY: 25574 AN XY: 74234

African (AFR) AF: 0.549 AC: 22722 AN: 41378

American (AMR) AF: 0.296 AC: 4523 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1444 AN: 5162

South Asian (SAS) AF: 0.336 AC: 1612 AN: 4804

European-Finnish (FIN) AF: 0.257 AC: 2708 AN: 10554

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17644 AN: 67940

Other (OTH) AF: 0.334 AC: 706 AN: 2114

Alfa AF: 0.310 Hom.: 1015

Bravo AF: 0.357

Asia WGS AF: 0.337 AC: 1168 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	8.6
DANN	Benign	0.53
PhyloP100		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8585; hg19: chr20-48698923; COSMIC: COSV59017302; COSMIC: COSV59017302;