rs34479552

Variant names:

• chr20-17616737-C-G
• rs34479552
• NM_001365613.2:c.3862G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-17616737-C-G
• chr20-17616737-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365613.2(RRBP1):​c.3862G>C​(p.Val1288Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1288I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RRBP1 NM_001365613.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030430406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRBP1	NM_001365613.2	c.3862G>C	p.Val1288Leu	missense_variant	Exon 21 of 25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2	c.2563G>C	p.Val855Leu	missense_variant	Exon 22 of 26		NP_001036041.2
RRBP1	NM_004587.3	c.2563G>C	p.Val855Leu	missense_variant	Exon 21 of 25		NP_004578.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRBP1	ENST00000377813.6	c.3862G>C	p.Val1288Leu	missense_variant	Exon 21 of 25	1	NM_001365613.2	ENSP00000367044.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.022
DANN	Benign	0.60
DEOGEN2	Benign	0.036	.;.;T;T;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.61	T;T;T;.;T;.;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.030	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	.;.;N;N;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.19	.;.;N;N;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.75	.;.;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0, 0.011	.;.;B;B;B;B;.
Vest4		0.075
MutPred		0.054		.;.;Loss of methylation at K1291 (P = 0.0693);Loss of methylation at K1291 (P = 0.0693);.;.;.;
MVP		0.24
MPC		0.20
ClinPred		0.019	T
GERP RS		-6.4
Varity_R		0.033
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs34479552; hg19: chr20-17597382;