Variant rs41281892 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000356286.10(RBCK1):c.144G>A(p.Glu48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 1,614,060 control chromosomes in the GnomAD database, including 1,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 94 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1333 hom. )

Consequence

RBCK1
ENST00000356286.10 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 20-410002-G-A is Benign according to our data. Variant chr20-410002-G-A is described in ClinVar as [Benign]. Clinvar id is 475182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-410002-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.01 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0501 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.144G>A	p.Glu48=	synonymous_variant	2/12	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.144G>A	p.Glu48=	synonymous_variant	2/12	1	NM_031229.4	ENSP00000348632	P1	Q9BYM8-1

Frequencies

GnomAD3 genomes

AF:

0.0304

AC:

4624

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0354

AC:

8875

AN:

251028

Hom.:

233

AF XY:

0.0378

AC XY:

5133

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0453

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.0556

Gnomad NFE exome

AF:

0.0420

Gnomad OTH exome

AF:

0.0392

GnomAD4 exome

AF:

0.0396

AC:

57825

AN:

1461790

Hom.:

1333

Cov.:

AF XY:

0.0399

AC XY:

29032

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00609

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.0440

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0514

Gnomad4 FIN exome

AF:

0.0569

Gnomad4 NFE exome

AF:

0.0411

Gnomad4 OTH exome

AF:

0.0386

GnomAD4 genome

AF:

0.0303

AC:

4621

AN:

152270

Hom.:

Cov.:

AF XY:

0.0302

AC XY:

2249

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00683

Gnomad4 AMR

AF:

0.0218

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0425

Gnomad4 FIN

AF:

0.0620

Gnomad4 NFE

AF:

0.0423

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0373

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0390

EpiControl

AF:

0.0392

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	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Polyglucosan body myopathy type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.8

DANN

Benign

0.56

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