chr1-229636946-T-G

Variant names:

• chr1-229636946-T-G
• rs3811473
• NM_014777.4:c.2333T>G

Variant summary

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

The NM_014777.4(URB2):​c.2333T>G​(p.Val778Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,613,694 control chromosomes in the GnomAD database, including 227,612 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.53 (21956 hom., cov: 34)
  • Exomes 𝑓: 0.53 (205656 hom.)
• Consequence: URB2 NM_014777.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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 (MetaRNN=1.988242E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
URB2	NM_014777.4	c.2333T>G	p.Val778Gly	missense_variant	Exon 4 of 10	ENST00000258243.7	NP_055592.2
URB2	NM_001314021.2	c.2333T>G	p.Val778Gly	missense_variant	Exon 4 of 10		NP_001300950.1
URB2	XM_005273360.3	c.2333T>G	p.Val778Gly	missense_variant	Exon 4 of 9		XP_005273417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
URB2	ENST00000258243.7	c.2333T>G	p.Val778Gly	missense_variant	Exon 4 of 10	1	NM_014777.4	ENSP00000258243.2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81222 AN: 152022 Hom.: 21931 Cov.: 34

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.529

GnomAD3 exomes AF: 0.560 AC: 140545 AN: 251004 Hom.: 40296 AF XY: 0.555 AC XY: 75238 AN XY: 135682

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.664

Gnomad ASJ exome AF: 0.491

Gnomad EAS exome AF: 0.757

Gnomad SAS exome AF: 0.554

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.527 AC: 770296 AN: 1461554 Hom.: 205656 Cov.: 73 AF XY: 0.528 AC XY: 383855 AN XY: 727066

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.652

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.555

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.534 AC: 81302 AN: 152140 Hom.: 21956 Cov.: 34 AF XY: 0.544 AC XY: 40460 AN XY: 74372

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.530

Alfa AF: 0.522 Hom.: 50733

Bravo AF: 0.535

TwinsUK AF: 0.502 AC: 1863

ALSPAC AF: 0.497 AC: 1917

ESP6500AA AF: 0.505 AC: 2223

ESP6500EA AF: 0.513 AC: 4410

ExAC AF: 0.551 AC: 66848

Asia WGS AF: 0.631 AC: 2190 AN: 3478

EpiCase AF: 0.517

EpiControl AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.10
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.037	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.016
Sift	Benign	0.95	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.11
ClinPred		0.0088	T
GERP RS		-2.1
Varity_R		0.030
gMVP		0.17

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: rs3811473; hg19: chr1-229772693; COSMIC: COSV51014159;