Variant chr15-42952501-A-G 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.4836-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,592,614 control chromosomes in the GnomAD database, including 360,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 27248 hom., cov: 32)

Exomes 𝑓: 0.67 ( 333118 hom. )

Consequence

UBR1
NM_174916.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.00

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=-0.81).

BP6

Variant 15-42952501-A-G is Benign according to our data. Variant chr15-42952501-A-G is described in ClinVar as [Benign]. Clinvar id is 1180324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBR1	NM_174916.3 linkuse as main transcript	c.4836-53T>C		intron_variant		ENST00000290650.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBR1	ENST00000290650.9 linkuse as main transcript	c.4836-53T>C		intron_variant		1	NM_174916.3	P1	Q8IWV7-1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83990

AN:

152032

Hom.:

27250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.561

Gnomad FIN

AF:

0.699

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.607

GnomAD4 exome

AF:

0.674

AC:

970725

AN:

1440464

Hom.:

333118

AF XY:

0.671

AC XY:

481843

AN XY:

718098

show subpopulations

Gnomad4 AFR exome

AF:

0.169

Gnomad4 AMR exome

AF:

0.716

Gnomad4 ASJ exome

AF:

0.648

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.543

Gnomad4 FIN exome

AF:

0.704

Gnomad4 NFE exome

AF:

0.701

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.552

AC:

83995

AN:

152150

Hom.:

27248

Cov.:

AF XY:

0.555

AC XY:

41239

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.688

Gnomad4 ASJ

AF:

0.646

Gnomad4 EAS

AF:

0.623

Gnomad4 SAS

AF:

0.560

Gnomad4 FIN

AF:

0.699

Gnomad4 NFE

AF:

0.705

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.678

Hom.:

69076

Bravo

AF:

0.535

Asia WGS

AF:

0.557

AC:

1937

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

DANN

Benign

0.63

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