rs461962

chr4-39722543-A-Cchr4-39722543-A-G

Variant summary

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

The NM_005339.5(UBE2K):c.64-14877A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,844 control chromosomes in the GnomAD database, including 9,268 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 0.31 (9268 hom., cov: 31)
• Consequence: UBE2K NM_005339.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

UBE2K (HGNC:4914): (ubiquitin conjugating enzyme E2 K) The protein encoded by this gene belongs to the ubiquitin-conjugating enzyme family. This protein interacts with RING finger proteins, and it can ubiquitinate huntingtin, the gene product for Huntington's disease. Known functions for this protein include a role in aggregate formation of expanded polyglutamine proteins and the suppression of apoptosis in polyglutamine diseases, a role in the dislocation of newly synthesized MHC class I heavy chains from the endoplasmic reticulum, and involvement in foam cell formation. Multiple transcript variants encoding different isoforms have been identified 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2K	NM_005339.5	c.64-14877A>C		intron_variant		ENST00000261427.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2K	ENST00000261427.10	c.64-14877A>C		intron_variant		1	NM_005339.5	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47626 AN: 151724 Hom.: 9240 Cov.: 31

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.314 AC: 47713 AN: 151844 Hom.: 9268 Cov.: 31 AF XY: 0.313 AC XY: 23249 AN XY: 74220

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.283

Alfa AF: 0.276 Hom.: 889

Bravo AF: 0.329

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.68

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: rs461962; hg19: chr4-39724163;