rs41281892

chr20-410002-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_031229.4(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 NM_031229.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

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]

ACMG classification

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	UniProt
RBCK1	NM_031229.4	c.144G>A	p.Glu48=	synonymous_variant	2/12	ENST00000356286.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBCK1	ENST00000356286.10	c.144G>A	p.Glu48=	synonymous_variant	2/12	1	NM_031229.4	P1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4624 AN: 152152 Hom.: 94 Cov.: 32

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

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.: 31 AF XY: 0.0399 AC XY: 29032 AN XY: 727200

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.: 94 Cov.: 32 AF XY: 0.0302 AC XY: 2249 AN XY: 74450

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.: 68

Bravo AF: 0.0264

Asia WGS AF: 0.0180 AC: 64 AN: 3478

EpiCase AF: 0.0390

EpiControl AF: 0.0392

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Polyglucosan body myopathy type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs41281892; hg19: chr20-390646;