chr20-17616086-C-T

Variant names:

• chr20-17616086-C-T
• rs2236250
• NM_001365613.2:c.3868-77G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRBP1	NM_001365613.2	MANE Select	c.3868-77G>A		intron	N/A	NP_001352542.1	Q9P2E9-1
	RRBP1	NM_001042576.2		c.2569-77G>A		intron	N/A	NP_001036041.2	Q9P2E9-3
	RRBP1	NM_004587.3		c.2569-77G>A		intron	N/A	NP_004578.3	Q9P2E9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRBP1	ENST00000377813.6	TSL:1 MANE Select	c.3868-77G>A		intron	N/A	ENSP00000367044.1	Q9P2E9-1
	RRBP1	ENST00000246043.8	TSL:1	c.3868-77G>A		intron	N/A	ENSP00000246043.4	Q9P2E9-1
	RRBP1	ENST00000360807.8	TSL:1	c.2569-77G>A		intron	N/A	ENSP00000354045.4	Q9P2E9-3

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90990 AN: 152040 Hom.: 31524 Cov.: 33

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

African (AFR) AF: 0.214 AC: 5409 AN: 25284

American (AMR) AF: 0.686 AC: 23314 AN: 33964

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 17502 AN: 21390

East Asian (EAS) AF: 0.479 AC: 16656 AN: 34802

South Asian (SAS) AF: 0.642 AC: 44889 AN: 69924

European-Finnish (FIN) AF: 0.782 AC: 27349 AN: 34954

Middle Eastern (MID) AF: 0.754 AC: 3714 AN: 4926

European-Non Finnish (NFE) AF: 0.763 AC: 588734 AN: 771734

Other (OTH) AF: 0.717 AC: 33164 AN: 46272

GnomAD4 genome AF: 0.598 AC: 91009 AN: 152158 Hom.: 31519 Cov.: 33 AF XY: 0.600 AC XY: 44627 AN XY: 74384

African (AFR) AF: 0.230 AC: 9551 AN: 41514

American (AMR) AF: 0.682 AC: 10444 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2827 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2555 AN: 5156

South Asian (SAS) AF: 0.627 AC: 3024 AN: 4824

European-Finnish (FIN) AF: 0.785 AC: 8330 AN: 10606

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52013 AN: 67962

Other (OTH) AF: 0.658 AC: 1390 AN: 2114

Alfa AF: 0.654 Hom.: 4663

Bravo AF: 0.575

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.63
PhyloP100		-2.1
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: rs2236250; hg19: chr20-17596731; COSMIC: COSV55697498;