rs6034866

Variant names:

• chr20-17623083-A-G
• rs6034866
• NM_001365613.2:c.3148-1136T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-17623083-A-G
• chr20-17623083-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365613.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRBP1	NM_001365613.2	MANE Select	c.3148-1136T>C		intron	N/A	NP_001352542.1
	RRBP1	NM_001042576.2		c.1849-1136T>C		intron	N/A	NP_001036041.2
	RRBP1	NM_004587.3		c.1849-1136T>C		intron	N/A	NP_004578.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRBP1	ENST00000377813.6	TSL:1 MANE Select	c.3148-1136T>C		intron	N/A	ENSP00000367044.1
	RRBP1	ENST00000246043.8	TSL:1	c.3148-1136T>C		intron	N/A	ENSP00000246043.4
	RRBP1	ENST00000360807.8	TSL:1	c.1849-1136T>C		intron	N/A	ENSP00000354045.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.875 AC: 7 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.938 AC: 15 AN: 16

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.216 AC: 8981 AN: 41546

American (AMR) AF: 0.823 AC: 12585 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3174 AN: 3470

East Asian (EAS) AF: 0.924 AC: 4754 AN: 5144

South Asian (SAS) AF: 0.942 AC: 4549 AN: 4828

European-Finnish (FIN) AF: 0.939 AC: 9973 AN: 10622

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62523 AN: 67994

Other (OTH) AF: 0.780 AC: 1648 AN: 2114

Alfa AF: 0.868 Hom.: 78282

Bravo AF: 0.685

Asia WGS AF: 0.868 AC: 3018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-0.10
PromoterAI		-0.0066	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6034866; hg19: chr20-17603728;