Variant 20-17615510-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001365613.2(RRBP1):c.3971G>A(p.Arg1324Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,605,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1324L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

RRBP1
NM_001365613.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.248

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03517437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRBP1	NM_001365613.2 link	c.3971G>A	p.Arg1324Gln	missense_variant	23/25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2 link	c.2672G>A	p.Arg891Gln	missense_variant	24/26		NP_001036041.2	Q9P2E9-3
RRBP1	NM_004587.3 link	c.2672G>A	p.Arg891Gln	missense_variant	23/25		NP_004578.3	Q9P2E9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6 link	c.3971G>A	p.Arg1324Gln	missense_variant	23/25	1	NM_001365613.2	ENSP00000367044.1		Q9P2E9-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000831

AC:

AN:

240544

Hom.:

AF XY:

0.0000536

AC XY:

AN XY:

130592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000164

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000128

AC:

186

AN:

1453128

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

722852

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000707

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000105

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000141

Hom.:

3115

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.039

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

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.77

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

M_CAP

Benign

0.043

MetaRNN

Benign

0.035

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

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

PrimateAI

Benign

0.29

PROVEAN

Benign

0.10

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

REVEL

Benign

0.033

Sift

Benign

0.37

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

Sift4G

Benign

0.15

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

Polyphen

0.0030, 0.033

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

Vest4

0.099

MutPred

0.12

.;.;Loss of phosphorylation at S1321 (P = 0.115);Loss of phosphorylation at S1321 (P = 0.115);.;.;.;

MVP

0.24

MPC

0.26

ClinPred

0.053

GERP RS

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.040

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