Variant chr20-408812-C-T 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_031229.4(RBCK1):c.22+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,598,886 control chromosomes in the GnomAD database, including 189,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15837 hom., cov: 34)

Exomes 𝑓: 0.49 ( 173996 hom. )

Consequence

RBCK1
NM_031229.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.282

Variant links:

Genes affected

RBCK1 (HGNC:15864): (RANBP2-type and C3HC4-type zinc finger containing 1) Enables several functions, including identical protein binding activity; protein sequestering activity; and ubiquitin binding activity. Involved in several processes, including T cell receptor signaling pathway; cellular protein metabolic process; and regulation of DNA-binding transcription factor activity. Part of LUBAC complex. Implicated in glycogen storage disease. [provided by Alliance of Genome Resources, Apr 2022]

RBCK1 links:

RBCK1 (HGNC:):

RBCK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 20-408812-C-T is Benign according to our data. Variant chr20-408812-C-T is described in ClinVar as [Benign]. Clinvar id is 1185505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBCK1	NM_031229.4 linkuse as main transcript	c.22+33C>T		intron_variant		ENST00000356286.10	NP_112506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBCK1	ENST00000356286.10 linkuse as main transcript	c.22+33C>T		intron_variant		1	NM_031229.4	ENSP00000348632.6		Q9BYM8-1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68531

AN:

152102

Hom.:

15824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.460

GnomAD3 exomes

AF:

0.448

AC:

99570

AN:

222236

Hom.:

22761

AF XY:

0.451

AC XY:

54459

AN XY:

120758

show subpopulations

Gnomad AFR exome

AF:

0.377

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.333

Gnomad SAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.575

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.487

AC:

704843

AN:

1446666

Hom.:

173996

Cov.:

AF XY:

0.484

AC XY:

347975

AN XY:

718600

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.568

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.462

GnomAD4 genome

AF:

0.450

AC:

68572

AN:

152220

Hom.:

15837

Cov.:

AF XY:

0.452

AC XY:

33603

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.381

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.462

Alfa

AF:

0.475

Hom.:

18674

Bravo

AF:

0.432

Asia WGS

AF:

0.385

AC:

1339

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. -

Polyglucosan body myopathy type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.2

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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