1-229635725-A-G

Position:

• chr1-229635725-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014777.4(URB2):​c.1112A>G​(p.Asn371Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: URB2 NM_014777.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04651326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
URB2	NM_014777.4	c.1112A>G	p.Asn371Ser	missense_variant	4/10	ENST00000258243.7
URB2	NM_001314021.2	c.1112A>G	p.Asn371Ser	missense_variant	4/10
URB2	XM_005273360.3	c.1112A>G	p.Asn371Ser	missense_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
URB2	ENST00000258243.7	c.1112A>G	p.Asn371Ser	missense_variant	4/10	1	NM_014777.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.3
DANN	Benign	0.56
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.91	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.038
Sift	Benign	0.14	T
Sift4G	Benign	0.084	T
Polyphen		0.013	B
Vest4		0.064
MutPred		0.24		Gain of helix (P = 0.062);
MVP		0.12
MPC		0.066
ClinPred		0.11	T
GERP RS		0.13
Varity_R		0.038
gMVP		0.093

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-229771472;