rs880987

Positions:

• chr21-43804574-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003683.6(RRP1):​c.*800C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,310 control chromosomes in the GnomAD database, including 2,960 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 0.17 (2956 hom., cov: 33)
  • Exomes 𝑓: 0.17 (4 hom.)
• Consequence: RRP1 NM_003683.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP1	NM_003683.6	c.*800C>T		3_prime_UTR_variant	13/13	ENST00000497547.2	NP_003674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP1	ENST00000497547.2	c.*800C>T		3_prime_UTR_variant	13/13	1	NM_003683.6	ENSP00000417464	P1
RRP1	ENST00000467112.5	n.2300C>T		non_coding_transcript_exon_variant	10/10	1
RRP1	ENST00000471909.1	n.1825C>T		non_coding_transcript_exon_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25786 AN: 152086 Hom.: 2946 Cov.: 33

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.170 AC: 18 AN: 106 Hom.: 4 Cov.: 0 AF XY: 0.118 AC XY: 9 AN XY: 76

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.170 AC: 25809 AN: 152204 Hom.: 2956 Cov.: 33 AF XY: 0.177 AC XY: 13170 AN XY: 74382

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.179

Alfa AF: 0.163 Hom.: 392

Bravo AF: 0.168

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.56

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: rs880987; hg19: chr21-45224455;