20-417634-G-T

Variant names:

• chr20-417634-G-T
• rs11698154
• NM_031229.4:c.261+15G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.385

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 -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 rank	MANE	Protein	UniProt
RBCK1	NM_031229.4	c.261+15G>T		intron_variant	Intron 3 of 11	ENST00000356286.10	NP_112506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBCK1	ENST00000356286.10	c.261+15G>T		intron_variant	Intron 3 of 11	1	NM_031229.4	ENSP00000348632.6

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22230 AN: 152028 Hom.: 1845 Cov.: 32

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

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.: 33 AF XY: 0.161 AC XY: 116470 AN XY: 725168

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.: 32 AF XY: 0.145 AC XY: 10768 AN XY: 74374

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

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polyglucosan body myopathy type 1 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs11698154; hg19: chr20-398278;