rs4924704

chr15-43059843-G-Achr15-43059843-G-Cchr15-43059843-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_174916.3(UBR1):c.862-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,613,096 control chromosomes in the GnomAD database, including 615,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (55913 hom., cov: 30)
  • Exomes 𝑓: 0.87 (559316 hom.)
• Consequence: UBR1 NM_174916.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.983

Genes affected

UBR1 (HGNC:16808): (ubiquitin protein ligase E3 component n-recognin 1) The N-end rule pathway is one proteolytic pathway of the ubiquitin system. The recognition component of this pathway, encoded by this gene, binds to a destabilizing N-terminal residue of a substrate protein and participates in the formation of a substrate-linked multiubiquitin chain. This leads to the eventual degradation of the substrate protein. The protein described in this record has a RING-type zinc finger and a UBR-type zinc finger. Mutations in this gene have been associated with Johanson-Blizzard syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-43059843-G-A is Benign according to our data. Variant chr15-43059843-G-A is described in ClinVar as [Benign]. Clinvar id is 262898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43059843-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR1	NM_174916.3	c.862-18C>T		intron_variant		ENST00000290650.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR1	ENST00000290650.9	c.862-18C>T		intron_variant		1	NM_174916.3	P1
UBR1	ENST00000546274.6	c.862-18C>T		intron_variant		2
UBR1	ENST00000563239.1	c.*202+11056C>T		intron_variant, NMD_transcript_variant		3
UBR1	ENST00000569971.5			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130236 AN: 152022 Hom.: 55885 Cov.: 30

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.868

GnomAD3 exomes AF: 0.863 AC: 216337 AN: 250780 Hom.: 93503 AF XY: 0.867 AC XY: 117693 AN XY: 135672

Gnomad AFR exome AF: 0.802

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.897

Gnomad EAS exome AF: 0.797

Gnomad SAS exome AF: 0.881

Gnomad FIN exome AF: 0.869

Gnomad NFE exome AF: 0.881

Gnomad OTH exome AF: 0.888

GnomAD4 exome AF: 0.874 AC: 1277593 AN: 1460956 Hom.: 559316 Cov.: 45 AF XY: 0.876 AC XY: 636478 AN XY: 726826

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.899

Gnomad4 EAS exome AF: 0.795

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.870

Gnomad4 NFE exome AF: 0.880

Gnomad4 OTH exome AF: 0.878

GnomAD4 genome AF: 0.857 AC: 130315 AN: 152140 Hom.: 55913 Cov.: 30 AF XY: 0.856 AC XY: 63654 AN XY: 74388

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.862

Alfa AF: 0.876 Hom.: 11914

Bravo AF: 0.851

Asia WGS AF: 0.826 AC: 2871 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Johanson-Blizzard syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.1
Dann	Benign	0.34

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: rs4924704; hg19: chr15-43352041; COSMIC: COSV51930102; COSMIC: COSV51930102;