rs2838378

Positions:

• chr21-43797678-T-C
• chr21-43797678-T-G
• chr21-43797678-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003683.6(RRP1):​c.600T>C​(p.Ile200Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,613,566 control chromosomes in the GnomAD database, including 201,027 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.

• Frequency:
  • Genomes: 𝑓 0.58 (27610 hom., cov: 32)
  • Exomes 𝑓: 0.47 (173417 hom.)
• Consequence: RRP1 NM_003683.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

Genes affected

RRP1 (HGNC:18785): (ribosomal RNA processing 1) The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA. [provided by RefSeq, Jul 2008]

RRP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP1	NM_003683.6	c.600T>C	p.Ile200Ile	synonymous_variant	7/13	ENST00000497547.2	NP_003674.1
RRP1	XM_017028485.3	c.600T>C	p.Ile200Ile	synonymous_variant	7/13		XP_016883974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP1	ENST00000497547.2	c.600T>C	p.Ile200Ile	synonymous_variant	7/13	1	NM_003683.6	ENSP00000417464.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87637 AN: 151900 Hom.: 27556 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.559

GnomAD3 exomes AF: 0.564 AC: 140497 AN: 249106 Hom.: 42713 AF XY: 0.556 AC XY: 75112 AN XY: 135204

Gnomad AFR exome AF: 0.811

Gnomad AMR exome AF: 0.740

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.751

Gnomad SAS exome AF: 0.723

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.432

Gnomad OTH exome AF: 0.522

GnomAD4 exome AF: 0.473 AC: 690960 AN: 1461548 Hom.: 173417 Cov.: 56 AF XY: 0.478 AC XY: 347606 AN XY: 727108

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.727

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.764

Gnomad4 SAS exome AF: 0.718

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome AF: 0.577 AC: 87746 AN: 152018 Hom.: 27610 Cov.: 32 AF XY: 0.583 AC XY: 43317 AN XY: 74312

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.565

Alfa AF: 0.469 Hom.: 21065

Bravo AF: 0.600

Asia WGS AF: 0.751 AC: 2610 AN: 3478

EpiCase AF: 0.429

EpiControl AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2838378; hg19: chr21-45217559; COSMIC: COSV71856776; COSMIC: COSV71856776;