Genetic Variant RRBP1:c.3868-77G>A (chr20-17616086-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001365613.2(RRBP1):c.3868-77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,195,408 control chromosomes in the GnomAD database, including 315,272 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: 𝑓 0.60 ( 31519 hom., cov: 33)

Exomes 𝑓: 0.73 ( 283753 hom. )

Consequence

RRBP1
NM_001365613.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

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 (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RRBP1	NM_001365613.2 link	c.3868-77G>A	intron_variant	Intron 21 of 24	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2 link	c.2569-77G>A	intron_variant	Intron 22 of 25		NP_001036041.2	Q9P2E9-3
RRBP1	NM_004587.3 link	c.2569-77G>A	intron_variant	Intron 21 of 24		NP_004578.3	Q9P2E9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6 link	c.3868-77G>A		intron_variant	Intron 21 of 24	1	NM_001365613.2	ENSP00000367044.1		Q9P2E9-1

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90990

AN:

152040

Hom.:

31524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.715

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.815

Gnomad EAS

AF:

0.496

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.785

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.765

Gnomad OTH

AF:

0.661

GnomAD4 exome

AF:

0.729

AC:

760731

AN:

1043250

Hom.:

283753

AF XY:

0.728

AC XY:

383943

AN XY:

527136

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.686

Gnomad4 ASJ exome

AF:

0.818

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.642

Gnomad4 FIN exome

AF:

0.782

Gnomad4 NFE exome

AF:

0.763

Gnomad4 OTH exome

AF:

0.717

GnomAD4 genome

AF:

0.598

AC:

91009

AN:

152158

Hom.:

31519

Cov.:

AF XY:

0.600

AC XY:

44627

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.682

Gnomad4 ASJ

AF:

0.815

Gnomad4 EAS

AF:

0.496

Gnomad4 SAS

AF:

0.627

Gnomad4 FIN

AF:

0.785

Gnomad4 NFE

AF:

0.765

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.672

Hom.:

4641

Bravo

AF:

0.575

Asia WGS

AF:

0.594

AC:

2067

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.34

DANN

Benign

0.63

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