rs6696978

Variant names:

• chr1-10149499-A-G
• rs6696978
• NM_001105562.3:c.2690+217A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.81).
• 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 rank	MANE	Protein	UniProt
UBE4B	NM_001105562.3	c.2690+217A>G		intron_variant	Intron 20 of 27	ENST00000343090.11	NP_001099032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE4B	ENST00000343090.11	c.2690+217A>G		intron_variant	Intron 20 of 27	1	NM_001105562.3	ENSP00000343001.6
UBE4B	ENST00000253251.12	c.2303+217A>G		intron_variant	Intron 19 of 26	1		ENSP00000253251.8
UBE4B	ENST00000672724.1	c.2843+217A>G		intron_variant	Intron 21 of 28			ENSP00000500453.1

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

African (AFR) AF: 0.139 AC: 5771 AN: 41512

American (AMR) AF: 0.333 AC: 5085 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3472

East Asian (EAS) AF: 0.108 AC: 560 AN: 5180

South Asian (SAS) AF: 0.161 AC: 776 AN: 4830

European-Finnish (FIN) AF: 0.231 AC: 2439 AN: 10572

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18867 AN: 67974

Other (OTH) AF: 0.246 AC: 519 AN: 2106

Alfa AF: 0.270 Hom.: 11102

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
PhyloP100		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: rs6696978; hg19: chr1-10209557;