rs3790310

Positions:

• chr20-17652178-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365613.2(RRBP1):​c.1912+6418T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,240 control chromosomes in the GnomAD database, including 1,627 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 0.13 (1627 hom., cov: 33)
• Consequence: RRBP1 NM_001365613.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRBP1	NM_001365613.2	c.1912+6418T>A		intron_variant		ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2	c.613+6427T>A		intron_variant			NP_001036041.2
RRBP1	NM_004587.3	c.613+6427T>A		intron_variant			NP_004578.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6	c.1912+6418T>A		intron_variant		1	NM_001365613.2	ENSP00000367044	A2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20531 AN: 152122 Hom.: 1624 Cov.: 33

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.149

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20545 AN: 152240 Hom.: 1627 Cov.: 33 AF XY: 0.133 AC XY: 9899 AN XY: 74438

Gnomad4 AFR AF: 0.0455

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.147

Alfa AF: 0.156 Hom.: 226

Bravo AF: 0.135

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.019
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs3790310; hg19: chr20-17632823;