Variant 20-17615941-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001365613.2(RRBP1):c.3936G>A(p.Thr1312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,610,206 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 34)

Exomes 𝑓: 0.0010 ( 18 hom. )

Consequence

RRBP1
NM_001365613.2 synonymous

Scores

Clinical Significance

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

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]

RRBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 20-17615941-C-T is Benign according to our data. Variant chr20-17615941-C-T is described in ClinVar as [Benign]. Clinvar id is 710613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1532/152332) while in subpopulation AFR AF= 0.0349 (1450/41576). AF 95% confidence interval is 0.0334. There are 19 homozygotes in gnomad4. There are 703 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RRBP1	NM_001365613.2 linkuse as main transcript	c.3936G>A	p.Thr1312=	synonymous_variant	22/25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2 linkuse as main transcript	c.2637G>A	p.Thr879=	synonymous_variant	23/26		NP_001036041.2
RRBP1	NM_004587.3 linkuse as main transcript	c.2637G>A	p.Thr879=	synonymous_variant	22/25		NP_004578.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6 linkuse as main transcript	c.3936G>A	p.Thr1312=	synonymous_variant	22/25	1	NM_001365613.2	ENSP00000367044	A2	Q9P2E9-1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1531

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

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:

0.000147

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00271

AC:

672

AN:

248380

Hom.:

AF XY:

0.00208

AC XY:

280

AN XY:

134594

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.00203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.00103

AC:

1507

AN:

1457874

Hom.:

Cov.:

AF XY:

0.000867

AC XY:

629

AN XY:

725424

show subpopulations

Gnomad4 AFR exome

AF:

0.0320

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000144

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.0101

AC:

1532

AN:

152332

Hom.:

Cov.:

AF XY:

0.00944

AC XY:

703

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0349

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.000814

Hom.:

Bravo

AF:

0.0112

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.17

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over