chr20-17615941-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365613.2(RRBP1):​c.3936G>C​(p.Thr1312Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,610,218 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1312T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 34)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: RRBP1 NM_001365613.2 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRBP1	NM_001365613.2	c.3936G>C	p.Thr1312Thr	synonymous_variant	Exon 22 of 25	ENST00000377813.6	NP_001352542.1
RRBP1	NM_001042576.2	c.2637G>C	p.Thr879Thr	synonymous_variant	Exon 23 of 26		NP_001036041.2
RRBP1	NM_004587.3	c.2637G>C	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>C	p.Thr1312Thr	synonymous_variant	Exon 22 of 25	1	NM_001365613.2	ENSP00000367044.1

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 384 AN: 152220 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00861

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

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: 0.000103

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000676 AC: 168 AN: 248380 Hom.: 2 AF XY: 0.000461 AC XY: 62 AN XY: 134594

Gnomad AFR exome AF: 0.00894

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000302 AC: 440 AN: 1457880 Hom.: 1 Cov.: 31 AF XY: 0.000273 AC XY: 198 AN XY: 725428

Gnomad4 AFR exome AF: 0.00881

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000423

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152338 Hom.: 3 Cov.: 34 AF XY: 0.00255 AC XY: 190 AN XY: 74490

Gnomad4 AFR AF: 0.00868

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.00266

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.044
DANN	Benign	0.47

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; COSMIC: COSV55695572;