chr20-17616724-G-A

Variant names:

• chr20-17616724-G-A
• rs56102376
• NM_001365613.2:c.3867+8C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365613.2(RRBP1):​c.3867+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,594,136 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (123 hom., cov: 34)
  • Exomes 𝑓: 0.0023 (108 hom.)
• Consequence: RRBP1 NM_001365613.2 splice_region, intron
• Scores: Splicing: ADA: 0.0003269
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0840
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 20-17616724-G-A is Benign according to our data. Variant chr20-17616724-G-A is described in ClinVar as Benign. ClinVar VariationId is 781544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 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.3867+8C>T		splice_region intron	N/A	NP_001352542.1	Q9P2E9-1
	RRBP1	NM_001042576.2		c.2568+8C>T		splice_region intron	N/A	NP_001036041.2	Q9P2E9-3
	RRBP1	NM_004587.3		c.2568+8C>T		splice_region 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.3867+8C>T		splice_region intron	N/A	ENSP00000367044.1	Q9P2E9-1
	RRBP1	ENST00000246043.8	TSL:1	c.3867+8C>T		splice_region intron	N/A	ENSP00000246043.4	Q9P2E9-1
	RRBP1	ENST00000360807.8	TSL:1	c.2568+8C>T		splice_region intron	N/A	ENSP00000354045.4	Q9P2E9-3

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3366 AN: 152192 Hom.: 123 Cov.: 34

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00752

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00599 AC: 1458 AN: 243554 AF XY: 0.00438

Gnomad AFR exome AF: 0.0803

Gnomad AMR exome AF: 0.00390

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000244

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.00229 AC: 3304 AN: 1441826 Hom.: 108 Cov.: 30 AF XY: 0.00191 AC XY: 1372 AN XY: 718388

African (AFR) AF: 0.0781 AC: 2555 AN: 32726

American (AMR) AF: 0.00403 AC: 174 AN: 43156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25800

East Asian (EAS) AF: 0.00 AC: 0 AN: 39398

South Asian (SAS) AF: 0.000199 AC: 17 AN: 85536

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51474

Middle Eastern (MID) AF: 0.00245 AC: 14 AN: 5704

European-Non Finnish (NFE) AF: 0.000205 AC: 225 AN: 1098340

Other (OTH) AF: 0.00533 AC: 318 AN: 59692

GnomAD4 genome AF: 0.0221 AC: 3371 AN: 152310 Hom.: 123 Cov.: 34 AF XY: 0.0204 AC XY: 1519 AN XY: 74454

African (AFR) AF: 0.0769 AC: 3198 AN: 41574

American (AMR) AF: 0.00751 AC: 115 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68024

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0101 Hom.: 17

Bravo AF: 0.0250

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.7
DANN	Benign	0.58
PhyloP100		-0.084
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00033
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs56102376; hg19: chr20-17597369;