Variant 20-408636-G-A 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.-122G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,322,684 control chromosomes in the GnomAD database, including 1,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 88 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1058 hom. )

Consequence

RBCK1
NM_031229.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.872

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=-0.69).

BP6

Variant 20-408636-G-A is Benign according to our data. Variant chr20-408636-G-A is described in ClinVar as [Benign]. Clinvar id is 1255114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-408636-G-A is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0503 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.-122G>A		5_prime_UTR_variant	1/12	ENST00000356286.10	NP_112506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBCK1	ENST00000356286 linkuse as main transcript	c.-122G>A		5_prime_UTR_variant	1/12	1	NM_031229.4	ENSP00000348632.6		Q9BYM8-1

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4467

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00661

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0422

Gnomad FIN

AF:

0.0616

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0410

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.0388

AC:

45410

AN:

1170322

Hom.:

1058

Cov.:

AF XY:

0.0393

AC XY:

23092

AN XY:

587902

show subpopulations

Gnomad4 AFR exome

AF:

0.00629

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.0437

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.0517

Gnomad4 FIN exome

AF:

0.0564

Gnomad4 NFE exome

AF:

0.0403

Gnomad4 OTH exome

AF:

0.0369

GnomAD4 genome

AF:

0.0293

AC:

4464

AN:

152362

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

2173

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00659

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.0455

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0420

Gnomad4 FIN

AF:

0.0616

Gnomad4 NFE

AF:

0.0410

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0353

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.0180

AC:

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 23, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.1

DANN

Benign

0.92

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