4-39722543-A-C

Variant names:

• chr4-39722543-A-C
• rs461962
• NM_005339.5:c.64-14877A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005339.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2K	NM_005339.5	MANE Select	c.64-14877A>C		intron	N/A	NP_005330.1
	UBE2K	NM_001111112.2		c.64-14877A>C		intron	N/A	NP_001104582.1
	UBE2K	NM_001111113.2		c.63+24153A>C		intron	N/A	NP_001104583.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2K	ENST00000261427.10	TSL:1 MANE Select	c.64-14877A>C		intron	N/A	ENSP00000261427.5
	UBE2K	ENST00000445950.2	TSL:1	c.64-14877A>C		intron	N/A	ENSP00000390483.2
	UBE2K	ENST00000503368.5	TSL:1	c.63+24153A>C		intron	N/A	ENSP00000421203.1

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

African (AFR) AF: 0.562 AC: 23220 AN: 41340

American (AMR) AF: 0.242 AC: 3697 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5170

South Asian (SAS) AF: 0.211 AC: 1015 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2397 AN: 10526

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14192 AN: 67954

Other (OTH) AF: 0.283 AC: 597 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-1.7
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: rs461962; hg19: chr4-39724163;