rs7528979

Positions:

• chr1-10033399-C-T

Variant summary

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

The NM_001105562.3(UBE4B):​c.-272C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 354,894 control chromosomes in the GnomAD database, including 20,600 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 (14457 hom., cov: 33)
  • Exomes 𝑓: 0.21 (6143 hom.)
• Consequence: UBE4B NM_001105562.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

Genes affected

UBE4B (HGNC:12500): (ubiquitination factor E4B) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes an additional conjugation factor, E4, which is involved in multiubiquitin chain assembly. This gene is also the strongest candidate in the neuroblastoma tumor suppressor genes. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4B	NM_001105562.3	c.-272C>T		5_prime_UTR_variant	1/28	ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE4B	ENST00000343090.11	c.-272C>T		5_prime_UTR_variant	1/28	1	NM_001105562.3	ENSP00000343001
UBE4B	ENST00000253251.12	c.-272C>T		5_prime_UTR_variant	1/27	1		ENSP00000253251	P1
UBE4B	ENST00000377153.5	c.-272C>T		5_prime_UTR_variant	1/3	3		ENSP00000366358
UBE4B	ENST00000672724.1	c.-272C>T		5_prime_UTR_variant	1/29			ENSP00000500453

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53318 AN: 152052 Hom.: 14395 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.215 AC: 43570 AN: 202724 Hom.: 6143 Cov.: 3 AF XY: 0.210 AC XY: 21534 AN XY: 102686

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.351 AC: 53445 AN: 152170 Hom.: 14457 Cov.: 33 AF XY: 0.352 AC XY: 26202 AN XY: 74384

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.294

Alfa AF: 0.198 Hom.: 6047

Bravo AF: 0.359

Asia WGS AF: 0.437 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7528979; hg19: chr1-10093457;