rs951908

Positions:

• chr1-19173341-G-C

Variant summary

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

The NM_020765.3(UBR4):​c.3166-35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,612,628 control chromosomes in the GnomAD database, including 320,500 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.67 (34732 hom., cov: 32)
  • Exomes 𝑓: 0.62 (285768 hom.)
• Consequence: UBR4 NM_020765.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

Genes affected

UBR4 (HGNC:30313): (ubiquitin protein ligase E3 component n-recognin 4) The protein encoded by this gene is an E3 ubiquitin-protein ligase that interacts with the retinoblastoma-associated protein in the nucleus and with calcium-bound calmodulin in the cytoplasm. The encoded protein appears to be a cytoskeletal component in the cytoplasm and part of the chromatin scaffold in the nucleus. In addition, this protein is a target of the human papillomavirus type 16 E7 oncoprotein. [provided by RefSeq, Aug 2010]

UBR4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR4	NM_020765.3	c.3166-35C>G		intron_variant		ENST00000375254.8	NP_065816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR4	ENST00000375254.8	c.3166-35C>G		intron_variant		1	NM_020765.3	ENSP00000364403.3
UBR4	ENST00000419533.1	n.814-35C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101469 AN: 151954 Hom.: 34672 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.643

GnomAD3 exomes AF: 0.644 AC: 161162 AN: 250062 Hom.: 53327 AF XY: 0.630 AC XY: 85111 AN XY: 135168

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.791

Gnomad ASJ exome AF: 0.568

Gnomad EAS exome AF: 0.813

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.609

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.622 AC: 908681 AN: 1460556 Hom.: 285768 Cov.: 57 AF XY: 0.617 AC XY: 448228 AN XY: 726422

Gnomad4 AFR exome AF: 0.795

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.575

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.668 AC: 101585 AN: 152072 Hom.: 34732 Cov.: 32 AF XY: 0.665 AC XY: 49436 AN XY: 74338

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.643

Alfa AF: 0.629 Hom.: 5610

Bravo AF: 0.693

Asia WGS AF: 0.713 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.52
BranchPoint Hunter		0.0

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: rs951908; hg19: chr1-19499835;