20-409666-A-T

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.23-215A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 152,004 control chromosomes in the GnomAD database, including 661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (661 hom., cov: 32)
• Consequence: RBCK1 NM_031229.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.758

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=-0.73).
• BP6: Variant 20-409666-A-T is Benign according to our data. Variant chr20-409666-A-T is described in ClinVar as [Benign]. Clinvar id is 1248880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBCK1	NM_031229.4	c.23-215A>T		intron_variant		ENST00000356286.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBCK1	ENST00000356286.10	c.23-215A>T		intron_variant		1	NM_031229.4	P1

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13190 AN: 151886 Hom.: 664 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0868 AC: 13193 AN: 152004 Hom.: 661 Cov.: 32 AF XY: 0.0869 AC XY: 6462 AN XY: 74320

Gnomad4 AFR AF: 0.0604

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.0917

Gnomad4 OTH AF: 0.0881

Alfa AF: 0.0851 Hom.: 79

Bravo AF: 0.0847

Asia WGS AF: 0.183 AC: 635 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 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.2
Dann	Benign	0.88

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: rs6139104; hg19: chr20-390310;