Variant 20-417634-G-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.261+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,611,074 control chromosomes in the GnomAD database, including 22,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1842 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20297 hom. )

Consequence

RBCK1
NM_031229.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.385

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=-0.95).

BP6

Variant 20-417634-G-T is Benign according to our data. Variant chr20-417634-G-T is described in ClinVar as [Benign]. Clinvar id is 403367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-417634-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 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.261+15G>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.261+15G>T		intron_variant		1	NM_031229.4	ENSP00000348632.6		Q9BYM8-1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22230

AN:

152028

Hom.:

1845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.144

AC:

36062

AN:

250354

Hom.:

3060

AF XY:

0.145

AC XY:

19690

AN XY:

135354

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.000762

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.161

AC:

235085

AN:

1458928

Hom.:

20297

Cov.:

AF XY:

0.161

AC XY:

116470

AN XY:

725168

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.000581

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.146

AC:

22237

AN:

152146

Hom.:

1842

Cov.:

AF XY:

0.145

AC XY:

10768

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.171

Hom.:

3336

Bravo

AF:

0.146

Asia WGS

AF:

0.0550

AC:

194

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
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 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

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	- -

Polyglucosan body myopathy type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

7.0

DANN

Benign

0.76

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