NM_001365613.2:c.3936G>A

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
• Publications: 1 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 -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 VariationId 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 passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

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.3936G>A	p.Thr1312Thr	synonymous	Exon 22 of 25	NP_001352542.1	Q9P2E9-1
	RRBP1	NM_001042576.2		c.2637G>A	p.Thr879Thr	synonymous	Exon 23 of 26	NP_001036041.2	Q9P2E9-3
	RRBP1	NM_004587.3		c.2637G>A	p.Thr879Thr	synonymous	Exon 22 of 25	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.3936G>A	p.Thr1312Thr	synonymous	Exon 22 of 25	ENSP00000367044.1	Q9P2E9-1
	RRBP1	ENST00000246043.8	TSL:1	c.3936G>A	p.Thr1312Thr	synonymous	Exon 20 of 23	ENSP00000246043.4	Q9P2E9-1
	RRBP1	ENST00000360807.8	TSL:1	c.2637G>A	p.Thr879Thr	synonymous	Exon 22 of 25	ENSP00000354045.4	Q9P2E9-3

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

African (AFR) AF: 0.0320 AC: 1072 AN: 33472

American (AMR) AF: 0.00181 AC: 81 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49606

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1111886

Other (OTH) 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

African (AFR) AF: 0.0349 AC: 1450 AN: 41576

American (AMR) AF: 0.00366 AC: 56 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68020

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00129 Hom.: 1

Bravo AF: 0.0112

EpiCase AF: 0.000164

EpiControl AF: 0.000178

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	-0.67
CADD	Benign	0.17
DANN	Benign	0.46
PhyloP100		-4.4
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

Other links and lift over

dbSNP: rs11551704; hg19: chr20-17596586;