chr20-417634-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• polyglucosan body myopathy 1 with or without immunodeficiency

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polyglucosan body myopathy type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 403367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031229.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBCK1	NM_031229.4	MANE Select	c.261+15G>T		intron	N/A	NP_112506.2	Q9BYM8-1
	RBCK1	NM_001410770.1		c.312+15G>T		intron	N/A	NP_001397699.1	A0A8V8TMZ2
	RBCK1	NM_006462.6		c.135+15G>T		intron	N/A	NP_006453.1	Q9BYM8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBCK1	ENST00000356286.10	TSL:1 MANE Select	c.261+15G>T		intron	N/A	ENSP00000348632.6	Q9BYM8-1
	RBCK1	ENST00000353660.7	TSL:1	c.135+15G>T		intron	N/A	ENSP00000254960.5	Q9BYM8-3
	RBCK1	ENST00000382181.2	TSL:1	n.135+15G>T		intron	N/A	ENSP00000371616.3	Q9BYM8-4

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

GnomAD2 exomes AF: 0.144 AC: 36062 AN: 250354 AF XY: 0.145

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 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

African (AFR) AF: 0.106 AC: 3546 AN: 33428

American (AMR) AF: 0.127 AC: 5654 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6938 AN: 26116

East Asian (EAS) AF: 0.000581 AC: 23 AN: 39612

South Asian (SAS) AF: 0.104 AC: 8936 AN: 86204

European-Finnish (FIN) AF: 0.148 AC: 7871 AN: 53272

Middle Eastern (MID) AF: 0.232 AC: 1334 AN: 5760

European-Non Finnish (NFE) AF: 0.172 AC: 190790 AN: 1109668

Other (OTH) AF: 0.166 AC: 9993 AN: 60224

GnomAD4 genome AF: 0.146 AC: 22237 AN: 152146 Hom.: 1842 Cov.: 32 AF XY: 0.145 AC XY: 10768 AN XY: 74374

African (AFR) AF: 0.109 AC: 4529 AN: 41514

American (AMR) AF: 0.146 AC: 2234 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5182

South Asian (SAS) AF: 0.103 AC: 496 AN: 4816

European-Finnish (FIN) AF: 0.156 AC: 1655 AN: 10582

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11735 AN: 67970

Other (OTH) AF: 0.172 AC: 365 AN: 2116

Alfa AF: 0.170 Hom.: 4045

Bravo AF: 0.146

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Polyglucosan body myopathy type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.0
DANN	Benign	0.76
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11698154; hg19: chr20-398278;