20-17615941-C-T

Variant names:

• chr20-17615941-C-T
• rs11551704
• NM_001365613.2:c.3936G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001365613.2(RRBP1):​c.3936G>A​(p.Thr1312Thr) 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -21 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_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 34. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRBP1	NM_001365613.2	c.3936G>A	p.Thr1312Thr	synonymous_variant	Exon 22 of 25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2	c.2637G>A	p.Thr879Thr	synonymous_variant	Exon 23 of 26		NP_001036041.2
RRBP1	NM_004587.3	c.2637G>A	p.Thr879Thr	synonymous_variant	Exon 22 of 25		NP_004578.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6	c.3936G>A	p.Thr1312Thr	synonymous_variant	Exon 22 of 25	1	NM_001365613.2	ENSP00000367044.1

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

GnomAD2 exomes AF: 0.00271 AC: 672 AN: 248380 AF XY: 0.00208

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 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 AC: 1072 AN: 33472

Gnomad4 AMR exome AF: 0.00181 AC: 81 AN: 44702

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26132

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000301 AC: 26 AN: 86248

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49606

Gnomad4 NFE exome AF: 0.000144 AC: 160 AN: 1111886

Gnomad4 Remaining exome AF: 0.00270 AC: 163 AN: 60364

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 AC: 0.0348759 AN: 0.0348759

Gnomad4 AMR AF: 0.00366 AC: 0.0036587 AN: 0.0036587

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000147 AC: 0.000147016 AN: 0.000147016

Gnomad4 OTH AF: 0.00756 AC: 0.00756144 AN: 0.00756144

Alfa AF: 0.00129 Hom.: 1

Bravo AF: 0.0112

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
Mutation Taster		=100/0	polymorphism

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;