rs6034866

Positions:

• chr20-17623083-A-G
• chr20-17623083-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.3148-1136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,238 control chromosomes in the GnomAD database, including 46,721 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 0.72 (46711 hom., cov: 33)
  • Exomes 𝑓: 0.88 (10 hom.)
• Consequence: RRBP1 NM_001365613.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRBP1	NM_001365613.2	c.3148-1136T>C		intron_variant		ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2	c.1849-1136T>C		intron_variant			NP_001036041.2
RRBP1	NM_004587.3	c.1849-1136T>C		intron_variant			NP_004578.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6	c.3148-1136T>C		intron_variant		1	NM_001365613.2	ENSP00000367044.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109310 AN: 152094 Hom.: 46701 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.778

GnomAD4 exome AF: 0.885 AC: 23 AN: 26 Hom.: 10 Cov.: 0 AF XY: 1.00 AC XY: 16 AN XY: 16

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.938

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.718 AC: 109337 AN: 152212 Hom.: 46711 Cov.: 33 AF XY: 0.726 AC XY: 54034 AN XY: 74420

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.780

Alfa AF: 0.881 Hom.: 46052

Bravo AF: 0.685

Asia WGS AF: 0.868 AC: 3018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.70

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: rs6034866; hg19: chr20-17603728;