rs2838386

chr21-43804303-A-Gchr21-43804303-A-Tchr21-43804303-A-C

Variant summary

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

The NM_003683.6(RRP1):c.*529A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,500 control chromosomes in the GnomAD database, including 27,963 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 (27914 hom., cov: 33)
  • Exomes 𝑓: 0.48 (49 hom.)
• Consequence: RRP1 NM_003683.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRP1	NM_003683.6	c.*529A>G		3_prime_UTR_variant	13/13	ENST00000497547.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRP1	ENST00000497547.2	c.*529A>G		3_prime_UTR_variant	13/13	1	NM_003683.6	P1
RRP1	ENST00000467112.5	n.2029A>G		non_coding_transcript_exon_variant	10/10	1
RRP1	ENST00000471909.1	n.1554A>G		non_coding_transcript_exon_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88253 AN: 152010 Hom.: 27861 Cov.: 33

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.478 AC: 177 AN: 370 Hom.: 49 Cov.: 0 AF XY: 0.472 AC XY: 102 AN XY: 216

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.581 AC: 88362 AN: 152130 Hom.: 27914 Cov.: 33 AF XY: 0.586 AC XY: 43577 AN XY: 74348

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.569

Alfa AF: 0.529 Hom.: 3988

Bravo AF: 0.604

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.1
Dann	Benign	0.38

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: rs2838386; hg19: chr21-45224184;