rs763971799

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS1

The NM_031229.4(RBCK1):c.746A>G(p.Gln249Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000571 in 1,559,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

RBCK1
NM_031229.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.16

Publications

0 publications found

Variant links:

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

RBCK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 20-419721-A-G is Benign according to our data. Variant chr20-419721-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 573181.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000092 (14/152204) while in subpopulation AMR AF = 0.00085 (13/15290). AF 95% confidence interval is 0.000502. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBCK1	NM_031229.4	MANE Select	c.746A>G	p.Gln249Arg	missense	Exon 6 of 12	NP_112506.2	Q9BYM8-1
RBCK1	NM_001410770.1		c.797A>G	p.Gln266Arg	missense	Exon 6 of 12	NP_001397699.1	A0A8V8TMZ2
RBCK1	NM_006462.6		c.620A>G	p.Gln207Arg	missense	Exon 5 of 11	NP_006453.1	Q9BYM8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBCK1	ENST00000356286.10	TSL:1 MANE Select	c.746A>G	p.Gln249Arg	missense	Exon 6 of 12	ENSP00000348632.6	Q9BYM8-1
RBCK1	ENST00000353660.7	TSL:1	c.620A>G	p.Gln207Arg	missense	Exon 5 of 11	ENSP00000254960.5	Q9BYM8-3
RBCK1	ENST00000382181.2	TSL:1	n.620A>G		non_coding_transcript_exon	Exon 5 of 10	ENSP00000371616.3	Q9BYM8-4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000388

AC:

AN:

162560

AF XY:

0.000296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00236

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000533

AC:

AN:

1406944

Hom.:

Cov.:

AF XY:

0.0000445

AC XY:

AN XY:

695966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32360

American (AMR)

AF:

0.00197

AC:

AN:

38084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25260

East Asian (EAS)

AF:

0.00

AC:

AN:

36978

South Asian (SAS)

AF:

0.00

AC:

AN:

80590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087984

Other (OTH)

AF:

0.00

AC:

AN:

58540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.000850

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.000249

ExAC

AF:

0.000171

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Polyglucosan body myopathy type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.73

M_CAP

Benign

0.011

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

4.2

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.99

REVEL

Benign

0.064

Sift

Uncertain

0.013

Sift4G

Benign

0.17

Polyphen

0.94

Vest4

0.34

MutPred

0.27

Gain of MoRF binding (P = 0.0148)

MVP

0.32

MPC

0.45

ClinPred

0.17

GERP RS

3.6

Varity_R

0.13

gMVP

0.88

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over