rs3955545

chr1-229640306-C-T

Variant summary

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

The NM_014777.4(URB2):c.3634+2059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,050 control chromosomes in the GnomAD database, including 21,808 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 0.53 (21808 hom., cov: 32)
• Consequence: URB2 NM_014777.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

Genes affected

URB2 (HGNC:28967): (URB2 ribosome biogenesis homolog) Predicted to be involved in ribosome biogenesis. Located in aggresome; midbody; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
URB2	NM_014777.4	c.3634+2059C>T		intron_variant		ENST00000258243.7
URB2	NM_001314021.2	c.3634+2059C>T		intron_variant
URB2	XM_005273360.3	c.3634+2059C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
URB2	ENST00000258243.7	c.3634+2059C>T		intron_variant		1	NM_014777.4	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80941 AN: 151932 Hom.: 21785 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.533 AC: 81019 AN: 152050 Hom.: 21808 Cov.: 32 AF XY: 0.543 AC XY: 40320 AN XY: 74316

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.529

Alfa AF: 0.538 Hom.: 3468

Bravo AF: 0.533

Asia WGS AF: 0.631 AC: 2189 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	0.28
Dann	Benign	0.13

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: rs3955545; hg19: chr1-229776053;