rs6696978

Positions:

• chr1-10149499-A-G

Variant summary

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

The NM_001105562.3(UBE4B):​c.2690+217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,102 control chromosomes in the GnomAD database, including 4,533 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 0.23 (4533 hom., cov: 32)
• Consequence: UBE4B NM_001105562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE4B	NM_001105562.3	c.2690+217A>G		intron_variant		ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE4B	ENST00000343090.11	c.2690+217A>G		intron_variant		1	NM_001105562.3	ENSP00000343001
UBE4B	ENST00000253251.12	c.2303+217A>G		intron_variant		1		ENSP00000253251	P1
UBE4B	ENST00000672724.1	c.2843+217A>G		intron_variant				ENSP00000500453

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35325 AN: 151984 Hom.: 4536 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.232 AC: 35325 AN: 152102 Hom.: 4533 Cov.: 32 AF XY: 0.230 AC XY: 17074 AN XY: 74364

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.246

Alfa AF: 0.276 Hom.: 8334

Bravo AF: 0.240

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs6696978; hg19: chr1-10209557;