rs11551704

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001365613.2(RRBP1):ā€‹c.3936G>Cā€‹(p.Thr1312Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,610,218 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0025 ( 3 hom., cov: 34)
Exomes š‘“: 0.00030 ( 1 hom. )

Consequence

RRBP1
NM_001365613.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RRBP1NM_001365613.2 linkc.3936G>C p.Thr1312Thr synonymous_variant Exon 22 of 25 ENST00000377813.6 NP_001352542.1
RRBP1NM_001042576.2 linkc.2637G>C p.Thr879Thr synonymous_variant Exon 23 of 26 NP_001036041.2 Q9P2E9-3
RRBP1NM_004587.3 linkc.2637G>C p.Thr879Thr synonymous_variant Exon 22 of 25 NP_004578.3 Q9P2E9-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RRBP1ENST00000377813.6 linkc.3936G>C p.Thr1312Thr synonymous_variant Exon 22 of 25 1 NM_001365613.2 ENSP00000367044.1 Q9P2E9-1

Frequencies

GnomAD3 genomes
AF:
0.00252
AC:
384
AN:
152220
Hom.:
2
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00861
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000676
AC:
168
AN:
248380
Hom.:
2
AF XY:
0.000461
AC XY:
62
AN XY:
134594
show subpopulations
Gnomad AFR exome
AF:
0.00894
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000302
AC:
440
AN:
1457880
Hom.:
1
Cov.:
31
AF XY:
0.000273
AC XY:
198
AN XY:
725428
show subpopulations
Gnomad4 AFR exome
AF:
0.00881
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.00104
GnomAD4 genome
AF:
0.00255
AC:
388
AN:
152338
Hom.:
3
Cov.:
34
AF XY:
0.00255
AC XY:
190
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00868
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.00266
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.044
DANN
Benign
0.47

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.

Other links and lift over

dbSNP: rs11551704; hg19: chr20-17596586; COSMIC: COSV55695572; API