20-17615941-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001365613.2(RRBP1):c.3936G>A(p.Thr1312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,610,206 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (19 hom., cov: 34)
  • Exomes 𝑓: 0.0010 (18 hom.)
• Consequence: RRBP1 NM_001365613.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.42

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 20-17615941-C-T is Benign according to our data. Variant chr20-17615941-C-T is described in ClinVar as [Benign]. Clinvar id is 710613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.42 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1532/152332) while in subpopulation AFR AF= 0.0349 (1450/41576). AF 95% confidence interval is 0.0334. There are 19 homozygotes in gnomad4. There are 703 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRBP1	NM_001365613.2	c.3936G>A	p.Thr1312=	synonymous_variant	22/25	ENST00000377813.6
RRBP1	NM_001042576.2	c.2637G>A	p.Thr879=	synonymous_variant	23/26
RRBP1	NM_004587.3	c.2637G>A	p.Thr879=	synonymous_variant	22/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRBP1	ENST00000377813.6	c.3936G>A	p.Thr1312=	synonymous_variant	22/25	1	NM_001365613.2	A2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1531 AN: 152214 Hom.: 19 Cov.: 34

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00271 AC: 672 AN: 248380 Hom.: 11 AF XY: 0.00208 AC XY: 280 AN XY: 134594

Gnomad AFR exome AF: 0.0347

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.00103 AC: 1507 AN: 1457874 Hom.: 18 Cov.: 31 AF XY: 0.000867 AC XY: 629 AN XY: 725424

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000144

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.0101 AC: 1532 AN: 152332 Hom.: 19 Cov.: 34 AF XY: 0.00944 AC XY: 703 AN XY: 74490

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.000814 Hom.: 0

Bravo AF: 0.0112

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.17
Dann	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs11551704; hg19: chr20-17596586;