Variant chr15-43059843-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.983

Variant links:

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]

UBR1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
UBR1	NM_174916.3 linkuse as main transcript	c.862-18C>T		intron_variant		ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
UBR1	ENST00000290650.9 linkuse as main transcript	c.862-18C>T	intron_variant	1	NM_174916.3	ENSP00000290650.4	Q8IWV7-1
UBR1	ENST00000546274.6 linkuse as main transcript	c.862-18C>T	intron_variant	2		ENSP00000477932.1	A0A087WTJ9
UBR1	ENST00000563239.1 linkuse as main transcript	n.*202+11056C>T	intron_variant	3		ENSP00000456502.1	H3BS20
UBR1	ENST00000569971.5 linkuse as main transcript	n.-39C>T	upstream_gene_variant	4		ENSP00000455759.1	H3BQF8

Frequencies

GnomAD3 genomes

AF:

0.857

AC:

130236

AN:

152022

Hom.:

55885

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.876

AC XY:

636478

AN XY:

726826

show subpopulations

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.:

AF XY:

0.856

AC XY:

63654

AN XY:

74388

show subpopulations

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over