21-43804303-A-G

Variant names:

• chr21-43804303-A-G
• rs2838386
• ENST00000467112.5:n.2029A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000467112.5(RRP1):​n.2029A>G variant causes a non coding transcript exon 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 ENST00000467112.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 5 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 -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 rank	MANE	Protein	UniProt
RRP1	NM_003683.6	c.*529A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000497547.2	NP_003674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP1	ENST00000467112.5	n.2029A>G		non_coding_transcript_exon_variant	Exon 10 of 10	1
RRP1	ENST00000471909.1	n.1554A>G		non_coding_transcript_exon_variant	Exon 8 of 8	1
RRP1	ENST00000497547.2	c.*529A>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_003683.6	ENSP00000417464.1

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

African (AFR) AF: 0.875 AC: 7 AN: 8

American (AMR) AF: 0.667 AC: 4 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 0.800 AC: 8 AN: 10

South Asian (SAS) AF: 0.750 AC: 18 AN: 24

European-Finnish (FIN) AF: 0.385 AC: 30 AN: 78

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.449 AC: 96 AN: 214

Other (OTH) AF: 0.417 AC: 10 AN: 24

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

African (AFR) AF: 0.804 AC: 33401 AN: 41520

American (AMR) AF: 0.644 AC: 9840 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3470

East Asian (EAS) AF: 0.760 AC: 3930 AN: 5174

South Asian (SAS) AF: 0.727 AC: 3507 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4907 AN: 10562

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29187 AN: 67970

Other (OTH) AF: 0.569 AC: 1204 AN: 2116

Alfa AF: 0.536 Hom.: 4230

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
PhyloP100		-2.1
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2838386; hg19: chr21-45224184;