rs12709950

chr19-55402310-C-A

Variant summary

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

The NM_014501.3(UBE2S):c.343-548G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,188 control chromosomes in the GnomAD database, including 37,233 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 0.69 (37233 hom., cov: 33)
• Consequence: UBE2S NM_014501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

Genes affected

UBE2S (HGNC:17895): (ubiquitin conjugating enzyme E2 S) This gene encodes a member of the ubiquitin-conjugating enzyme family. The encoded protein is able to form a thiol ester linkage with ubiquitin in a ubiquitin activating enzyme-dependent manner, a characteristic property of ubiquitin carrier proteins. [provided by RefSeq, Jul 2008]

RPL28 (HGNC:10330): (ribosomal protein L28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L28E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2S	NM_014501.3	c.343-548G>T		intron_variant		ENST00000264552.14
RPL28	NM_001363697.1	c.325-633C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2S	ENST00000264552.14	c.343-548G>T		intron_variant		1	NM_014501.3	P1
RPL28	ENST00000560055.5	c.325-633C>A		intron_variant		3
UBE2S	ENST00000587845.5	c.430-548G>T		intron_variant		2
UBE2S	ENST00000589978.1	c.*26-548G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104569 AN: 152070 Hom.: 37181 Cov.: 33

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.688 AC: 104678 AN: 152188 Hom.: 37233 Cov.: 33 AF XY: 0.682 AC XY: 50697 AN XY: 74386

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.700

Alfa AF: 0.670 Hom.: 17184

Bravo AF: 0.693

Asia WGS AF: 0.522 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.50

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: rs12709950; hg19: chr19-55913678;