Variant 20-17624595-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001365613.2(RRBP1):c.3128T>A(p.Leu1043His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,592,674 control chromosomes in the GnomAD database, including 796,245 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 1.0 ( 76105 hom., cov: 33)

Exomes 𝑓: 1.0 ( 720140 hom. )

Consequence

RRBP1
NM_001365613.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.270

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.4000606E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRBP1	NM_001365613.2 linkuse as main transcript	c.3128T>A	p.Leu1043His	missense_variant	13/25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2 linkuse as main transcript	c.1829T>A	p.Leu610His	missense_variant	14/26		NP_001036041.2	Q9P2E9-3
RRBP1	NM_004587.3 linkuse as main transcript	c.1829T>A	p.Leu610His	missense_variant	13/25		NP_004578.3	Q9P2E9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6 linkuse as main transcript	c.3128T>A	p.Leu1043His	missense_variant	13/25	1	NM_001365613.2	ENSP00000367044.1		Q9P2E9-1

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

152143

AN:

152194

Hom.:

76046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

217443

AN:

217454

Hom.:

108716

AF XY:

1.00

AC XY:

116358

AN XY:

116362

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1440321

AN:

1440362

Hom.:

720140

Cov.:

AF XY:

1.00

AC XY:

714124

AN XY:

714140

show subpopulations

Gnomad4 AFR exome

AF:

0.999

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

1.00

AC:

152261

AN:

152312

Hom.:

76105

Cov.:

AF XY:

1.00

AC XY:

74447

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.999

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

0.995

Hom.:

7749

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

1.00

AC:

4403

ESP6500EA

AF:

1.00

AC:

8600

ExAC

AF:

1.00

AC:

120004

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.0

DANN

Benign

0.44

DEOGEN2

Benign

0.083

.;T;T;.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.0091

T;T;.;T;.;T

MetaRNN

Benign

5.4e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.84

.;N;N;.;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

1.3

.;N;N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.33

.;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;T

Polyphen

0.0

.;.;.;B;B;.

Vest4

0.093

MPC

0.13

ClinPred

0.00063

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.034

gMVP

0.094

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over