rs3955545

Variant names:

• chr1-229640306-C-T
• rs3955545
• NM_014777.4:c.3634+2059C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
URB2	NM_014777.4	c.3634+2059C>T		intron_variant	Intron 4 of 9	ENST00000258243.7	NP_055592.2
URB2	NM_001314021.2	c.3634+2059C>T		intron_variant	Intron 4 of 9		NP_001300950.1
URB2	XM_005273360.3	c.3634+2059C>T		intron_variant	Intron 4 of 8		XP_005273417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
URB2	ENST00000258243.7	c.3634+2059C>T		intron_variant	Intron 4 of 9	1	NM_014777.4	ENSP00000258243.2

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

African (AFR) AF: 0.505 AC: 20924 AN: 41474

American (AMR) AF: 0.591 AC: 9042 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1719 AN: 3468

East Asian (EAS) AF: 0.769 AC: 3973 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2751 AN: 4824

European-Finnish (FIN) AF: 0.567 AC: 5977 AN: 10540

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34951 AN: 67966

Other (OTH) AF: 0.529 AC: 1118 AN: 2112

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
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: rs3955545; hg19: chr1-229776053;