1-10130826-A-T

Variant names:

• chr1-10130826-A-T
• rs2295294
• NM_001105562.3:c.1911+13A>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.1911+13A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,609,586 control chromosomes in the GnomAD database, including 134,203 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 0.47 (17539 hom., cov: 32)
  • Exomes 𝑓: 0.40 (116664 hom.)
• Consequence: UBE4B NM_001105562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 11 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE4B	NM_001105562.3	c.1911+13A>T		intron_variant	Intron 14 of 27	ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE4B	ENST00000343090.11	c.1911+13A>T		intron_variant	Intron 14 of 27	1	NM_001105562.3	ENSP00000343001.6

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70648 AN: 151932 Hom.: 17509 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.441

GnomAD2 exomes AF: 0.420 AC: 105097 AN: 250144 AF XY: 0.410

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.412

Gnomad FIN exome AF: 0.357

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.397 AC: 578047 AN: 1457536 Hom.: 116664 Cov.: 31 AF XY: 0.395 AC XY: 286240 AN XY: 725354

African (AFR) AF: 0.649 AC: 21670 AN: 33406

American (AMR) AF: 0.500 AC: 22344 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 12071 AN: 26124

East Asian (EAS) AF: 0.375 AC: 14877 AN: 39680

South Asian (SAS) AF: 0.387 AC: 33372 AN: 86128

European-Finnish (FIN) AF: 0.358 AC: 19081 AN: 53328

Middle Eastern (MID) AF: 0.395 AC: 2276 AN: 5760

European-Non Finnish (NFE) AF: 0.386 AC: 427313 AN: 1108174

Other (OTH) AF: 0.416 AC: 25043 AN: 60234

GnomAD4 genome AF: 0.465 AC: 70727 AN: 152050 Hom.: 17539 Cov.: 32 AF XY: 0.462 AC XY: 34314 AN XY: 74316

African (AFR) AF: 0.646 AC: 26793 AN: 41476

American (AMR) AF: 0.473 AC: 7223 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1616 AN: 3464

East Asian (EAS) AF: 0.396 AC: 2052 AN: 5182

South Asian (SAS) AF: 0.384 AC: 1850 AN: 4822

European-Finnish (FIN) AF: 0.347 AC: 3673 AN: 10572

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25993 AN: 67960

Other (OTH) AF: 0.444 AC: 939 AN: 2114

Alfa AF: 0.415 Hom.: 2478

Bravo AF: 0.484

Asia WGS AF: 0.421 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		1.5
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: rs2295294; hg19: chr1-10190884; COSMIC: COSV53528852;