20-17615937-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001365613.2(RRBP1):c.3940G>A(p.Glu1314Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,610,044 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0034 ( 19 hom. )

Consequence

RRBP1
NM_001365613.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.06

Publications

7 publications found

Variant links:

Genes affected

RRBP1 (HGNC:10448): (ribosome binding protein 1) This gene encodes a ribosome-binding protein of the endoplasmic reticulum (ER) membrane. Studies suggest that this gene plays a role in ER proliferation, secretory pathways and secretory cell differentiation, and mediation of ER-microtubule interactions. Alternative splicing has been observed and protein isoforms are characterized by regions of N-terminal decapeptide and C-terminal heptad repeats. Splicing of the tandem repeats results in variations in ribosome-binding affinity and secretory function. The full-length nature of variants which differ in repeat length has not been determined. Pseudogenes of this gene have been identified on chromosomes 3 and 7, and RRBP1 has been excluded as a candidate gene in the cause of Alagille syndrome, the result of a mutation in a nearby gene on chromosome 20p12. [provided by RefSeq, Apr 2012]

RRBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006175071).

BP6

Variant 20-17615937-C-T is Benign according to our data. Variant chr20-17615937-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 712138.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365613.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RRBP1	NM_001365613.2	MANE Select	c.3940G>A	p.Glu1314Lys	missense	Exon 22 of 25	NP_001352542.1	Q9P2E9-1
RRBP1	NM_001042576.2		c.2641G>A	p.Glu881Lys	missense	Exon 23 of 26	NP_001036041.2	Q9P2E9-3
RRBP1	NM_004587.3		c.2641G>A	p.Glu881Lys	missense	Exon 22 of 25	NP_004578.3	Q9P2E9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RRBP1	ENST00000377813.6	TSL:1 MANE Select	c.3940G>A	p.Glu1314Lys	missense	Exon 22 of 25	ENSP00000367044.1	Q9P2E9-1
RRBP1	ENST00000246043.8	TSL:1	c.3940G>A	p.Glu1314Lys	missense	Exon 20 of 23	ENSP00000246043.4	Q9P2E9-1
RRBP1	ENST00000360807.8	TSL:1	c.2641G>A	p.Glu881Lys	missense	Exon 22 of 25	ENSP00000354045.4	Q9P2E9-3

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00354

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00238

AC:

590

AN:

248188

AF XY:

0.00243

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00925

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000995

Gnomad NFE exome

AF:

0.00306

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00335

AC:

4890

AN:

1457696

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

2480

AN XY:

725344

show subpopulations

African (AFR)

AF:

0.000597

AC:

AN:

33474

American (AMR)

AF:

0.00136

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00884

AC:

231

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00186

AC:

160

AN:

86240

European-Finnish (FIN)

AF:

0.00125

AC:

AN:

49470

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00369

AC:

4104

AN:

1111864

Other (OTH)

AF:

0.00399

AC:

241

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

226

453

679

906

1132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<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:

0.00234

AC:

356

AN:

152348

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41586

American (AMR)

AF:

0.00268

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00354

AC:

241

AN:

68018

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00308

Hom.:

Bravo

AF:

0.00251

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00213

AC:

259

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00385

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.7

PhyloP100

2.1

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.3

REVEL

Benign

0.24

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.55

MVP

0.56

MPC

0.29

ClinPred

0.030

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.38

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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