21-43797678-T-C

Variant names:

• chr21-43797678-T-C
• rs2838378
• NM_003683.6:c.600T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003683.6. 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
	RRP1	NM_003683.6	MANE Select	c.600T>C	p.Ile200Ile	synonymous	Exon 7 of 13	NP_003674.1	P56182

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1	ENST00000497547.2	TSL:1 MANE Select	c.600T>C	p.Ile200Ile	synonymous	Exon 7 of 13	ENSP00000417464.1	P56182
	RRP1	ENST00000467112.5	TSL:1	n.714T>C		non_coding_transcript_exon	Exon 4 of 10
	RRP1	ENST00000471909.1	TSL:1	n.239T>C		non_coding_transcript_exon	Exon 2 of 8

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

GnomAD2 exomes AF: 0.564 AC: 140497 AN: 249106 AF XY: 0.556

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 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

African (AFR) AF: 0.808 AC: 27059 AN: 33478

American (AMR) AF: 0.727 AC: 32512 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12629 AN: 26136

East Asian (EAS) AF: 0.764 AC: 30341 AN: 39700

South Asian (SAS) AF: 0.718 AC: 61935 AN: 86252

European-Finnish (FIN) AF: 0.464 AC: 24688 AN: 53194

Middle Eastern (MID) AF: 0.586 AC: 3381 AN: 5768

European-Non Finnish (NFE) AF: 0.421 AC: 467945 AN: 1111918

Other (OTH) AF: 0.505 AC: 30470 AN: 60380

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

African (AFR) AF: 0.803 AC: 33310 AN: 41468

American (AMR) AF: 0.638 AC: 9756 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3926 AN: 5172

South Asian (SAS) AF: 0.727 AC: 3505 AN: 4824

European-Finnish (FIN) AF: 0.463 AC: 4884 AN: 10556

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28833 AN: 67940

Other (OTH) AF: 0.565 AC: 1190 AN: 2106

Alfa AF: 0.483 Hom.: 28179

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.54
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2838378; hg19: chr21-45217559; COSMIC: COSV71856776; COSMIC: COSV71856776;