rs7528979

Variant names:

• chr1-10033399-C-T
• rs7528979
• NM_001105562.3:c.-272C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UBE4B	NM_001105562.3	c.-272C>T		5_prime_UTR_variant	Exon 1 of 28	ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE4B	ENST00000343090.11	c.-272C>T		5_prime_UTR_variant	Exon 1 of 28	1	NM_001105562.3	ENSP00000343001.6
UBE4B	ENST00000253251.12	c.-272C>T		5_prime_UTR_variant	Exon 1 of 27	1		ENSP00000253251.8
UBE4B	ENST00000672724.1	c.-272C>T		5_prime_UTR_variant	Exon 1 of 29			ENSP00000500453.1
UBE4B	ENST00000377153.5	c.-272C>T		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000366358.1

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

African (AFR) AF: 0.760 AC: 4755 AN: 6256

American (AMR) AF: 0.161 AC: 934 AN: 5798

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 1850 AN: 7804

East Asian (EAS) AF: 0.319 AC: 6010 AN: 18812

South Asian (SAS) AF: 0.342 AC: 995 AN: 2908

European-Finnish (FIN) AF: 0.236 AC: 3920 AN: 16616

Middle Eastern (MID) AF: 0.256 AC: 280 AN: 1092

European-Non Finnish (NFE) AF: 0.165 AC: 21426 AN: 129884

Other (OTH) AF: 0.251 AC: 3400 AN: 13554

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

African (AFR) AF: 0.756 AC: 31407 AN: 41520

American (AMR) AF: 0.179 AC: 2743 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1924 AN: 5176

South Asian (SAS) AF: 0.370 AC: 1782 AN: 4816

European-Finnish (FIN) AF: 0.258 AC: 2728 AN: 10588

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11184 AN: 67998

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.212 Hom.: 10959

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
PhyloP100		-0.33
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7528979; hg19: chr1-10093457;