Variant chr20-17616724-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365613.2(RRBP1):c.3867+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,594,136 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 123 hom., cov: 34)

Exomes 𝑓: 0.0023 ( 108 hom. )

Consequence

RRBP1
NM_001365613.2 splice_region, intron

Scores

Splicing: ADA: 0.0003269

Clinical Significance

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

Conservation

PhyloP100: -0.0840

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 20-17616724-G-A is Benign according to our data. Variant chr20-17616724-G-A is described in ClinVar as [Benign]. Clinvar id is 781544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RRBP1	NM_001365613.2 linkuse as main transcript	c.3867+8C>T	splice_region_variant, intron_variant	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2 linkuse as main transcript	c.2568+8C>T	splice_region_variant, intron_variant		NP_001036041.2
RRBP1	NM_004587.3 linkuse as main transcript	c.2568+8C>T	splice_region_variant, intron_variant		NP_004578.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6 linkuse as main transcript	c.3867+8C>T		splice_region_variant, intron_variant		1	NM_001365613.2	ENSP00000367044	A2	Q9P2E9-1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3366

AN:

152192

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0770

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00752

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:

0.000323

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00599

AC:

1458

AN:

243554

Hom.:

AF XY:

0.00438

AC XY:

579

AN XY:

132180

show subpopulations

Gnomad AFR exome

AF:

0.0803

Gnomad AMR exome

AF:

0.00390

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.00254

GnomAD4 exome

AF:

0.00229

AC:

3304

AN:

1441826

Hom.:

108

Cov.:

AF XY:

0.00191

AC XY:

1372

AN XY:

718388

show subpopulations

Gnomad4 AFR exome

AF:

0.0781

Gnomad4 AMR exome

AF:

0.00403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000199

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000205

Gnomad4 OTH exome

AF:

0.00533

GnomAD4 genome

AF:

0.0221

AC:

3371

AN:

152310

Hom.:

123

Cov.:

AF XY:

0.0204

AC XY:

1519

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0769

Gnomad4 AMR

AF:

0.00751

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.0250

Asia WGS

AF:

0.00433

AC:

AN:

3478

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

-0.69

CADD

Benign

3.7

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00033

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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