Variant rs138963231 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000290650.9(UBR1):c.4054-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,607,344 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 32)

Exomes 𝑓: 0.015 ( 227 hom. )

Consequence

UBR1
ENST00000290650.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001069

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.850

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 15-42983997-G-C is Benign according to our data. Variant chr15-42983997-G-C is described in ClinVar as [Benign]. Clinvar id is 262893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42983997-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0124 (1883/152176) while in subpopulation NFE AF= 0.0153 (1039/68008). AF 95% confidence interval is 0.0145. There are 33 homozygotes in gnomad4. There are 937 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR1	NM_174916.3 linkuse as main transcript	c.4054-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000290650.9	NP_777576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR1	ENST00000290650.9 linkuse as main transcript	c.4054-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_174916.3	ENSP00000290650	P1	Q8IWV7-1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1883

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00283

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.00863

GnomAD3 exomes

AF:

0.0131

AC:

3269

AN:

249586

Hom.:

AF XY:

0.0130

AC XY:

1750

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.0497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00224

Gnomad FIN exome

AF:

0.0338

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0152

AC:

22188

AN:

1455168

Hom.:

227

Cov.:

AF XY:

0.0150

AC XY:

10860

AN XY:

724258

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.00442

Gnomad4 ASJ exome

AF:

0.0484

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00293

Gnomad4 FIN exome

AF:

0.0365

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0124

AC:

1883

AN:

152176

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

937

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00282

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.0550

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0377

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.00854

Alfa

AF:

0.0162

Hom.:

Bravo

AF:

0.0103

EpiCase

AF:

0.0152

EpiControl

AF:

0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.1

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.10

SpliceAI score (max)

0.020

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