20-408274-G-C

Position:

• chr20-408274-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000353660.7(RBCK1):​c.-465G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 179,154 control chromosomes in the GnomAD database, including 512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (407 hom., cov: 32)
  • Exomes 𝑓: 0.066 (105 hom.)
• Consequence: RBCK1 ENST00000353660.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.789

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 20-408274-G-C is Benign according to our data. Variant chr20-408274-G-C is described in ClinVar as [Benign]. Clinvar id is 1256790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBCK1	NM_031229.4			upstream_gene_variant		ENST00000356286.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBCK1	ENST00000356286.10			upstream_gene_variant		1	NM_031229.4	P1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9403 AN: 151862 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0577

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0658 AC: 1787 AN: 27176 Hom.: 105 Cov.: 0 AF XY: 0.0742 AC XY: 1110 AN XY: 14962

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.0335

Gnomad4 ASJ exome AF: 0.0363

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0633

Gnomad4 NFE exome AF: 0.0441

Gnomad4 OTH exome AF: 0.0519

GnomAD4 genome AF: 0.0619 AC: 9405 AN: 151978 Hom.: 407 Cov.: 32 AF XY: 0.0643 AC XY: 4775 AN XY: 74276

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.0863

Gnomad4 NFE AF: 0.0577

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0593 Hom.: 44

Bravo AF: 0.0559

Asia WGS AF: 0.169 AC: 588 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.9
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144693124; hg19: chr20-388918;