20-17621719-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001365613.2(RRBP1):c.3295C>T(p.His1099Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00203 in 1,613,682 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 20 hom. )

Consequence

RRBP1
NM_001365613.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022284985).

BP6

Variant 20-17621719-G-A is Benign according to our data. Variant chr20-17621719-G-A is described in ClinVar as [Benign]. Clinvar id is 777534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1671/152382) while in subpopulation AFR AF = 0.0368 (1530/41584). AF 95% confidence interval is 0.0353. There are 25 homozygotes in GnomAd4. There are 825 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRBP1	NM_001365613.2 link	c.3295C>T	p.His1099Tyr	missense_variant	Exon 15 of 25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2 link	c.1996C>T	p.His666Tyr	missense_variant	Exon 16 of 26		NP_001036041.2	Q9P2E9-3
RRBP1	NM_004587.3 link	c.1996C>T	p.His666Tyr	missense_variant	Exon 15 of 25		NP_004578.3	Q9P2E9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6 link	c.3295C>T	p.His1099Tyr	missense_variant	Exon 15 of 25	1	NM_001365613.2	ENSP00000367044.1		Q9P2E9-1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1665

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0368

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.00294

AC:

735

AN:

249660

AF XY:

0.00212

show subpopulations

Gnomad AFR exome

AF:

0.0382

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00110

AC:

1611

AN:

1461300

Hom.:

Cov.:

AF XY:

0.000933

AC XY:

678

AN XY:

726978

show subpopulations

African (AFR)

AF:

0.0364

AC:

1220

AN:

33480

American (AMR)

AF:

0.00275

AC:

123

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52970

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000845

AC:

AN:

1111950

Other (OTH)

AF:

0.00252

AC:

152

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

175

262

350

437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0110

AC:

1671

AN:

152382

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

825

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.0368

AC:

1530

AN:

41584

American (AMR)

AF:

0.00686

AC:

105

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68042

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

169

254

338

423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00414

Hom.:

Bravo

AF:

0.0128

ESP6500AA

AF:

0.0402

AC:

177

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00377

AC:

458

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

.;.;T;T;.;.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.72

T;T;T;.;T;.;T

MetaRNN

Benign

0.0022

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;.;N;N;.;.;.

PhyloP100

3.7

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

.;.;N;N;N;N;N

REVEL

Benign

0.035

Sift

Uncertain

0.0080

.;.;D;D;D;D;D

Sift4G

Benign

0.19

T;D;D;D;D;D;D

Polyphen

0.0090, 0.21

.;.;B;B;B;B;.

Vest4

0.28

MVP

0.42

MPC

0.12

ClinPred

0.016

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.096

Mutation Taster

=95/5

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

Loading publications...

20-17621719-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over