20-408636-G-A

Position:

• chr20-408636-G-A

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.872

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=-0.69).
• 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_single_submitter, 1 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	UniProt
RBCK1	NM_031229.4	c.-122G>A		5_prime_UTR_variant	1/12	ENST00000356286.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBCK1	ENST00000356286.10	c.-122G>A		5_prime_UTR_variant	1/12	1	NM_031229.4	P1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4467 AN: 152244 Hom.: 88 Cov.: 32

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.: 16 AF XY: 0.0393 AC XY: 23092 AN XY: 587902

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.: 88 Cov.: 32 AF XY: 0.0292 AC XY: 2173 AN XY: 74506

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.: 15

Bravo AF: 0.0252

Asia WGS AF: 0.0180 AC: 62 AN: 3478

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 23, 2021

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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

Other links and lift over

dbSNP: rs41306771; hg19: chr20-389280;