rs4818868

Variant names:

• chr21-43802177-A-G
• rs4818868
• NM_003683.6:c.1010-97A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-43802177-A-G
• chr21-43802177-A-T

Variant summary

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

The NM_003683.6(RRP1):​c.1010-97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 814,122 control chromosomes in the GnomAD database, including 121,227 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 (27866 hom., cov: 30)
  • Exomes 𝑓: 0.51 (93361 hom.)
• Consequence: RRP1 NM_003683.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1	NM_003683.6	MANE Select	c.1010-97A>G		intron	N/A	NP_003674.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1	ENST00000497547.2	TSL:1 MANE Select	c.1010-97A>G		intron	N/A	ENSP00000417464.1
	RRP1	ENST00000467112.5	TSL:1	n.1124-97A>G		intron	N/A
	RRP1	ENST00000471909.1	TSL:1	n.649-97A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88104 AN: 151666 Hom.: 27813 Cov.: 30

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.513 AC: 340025 AN: 662338 Hom.: 93361 AF XY: 0.519 AC XY: 182852 AN XY: 352112

African (AFR) AF: 0.803 AC: 14596 AN: 18180

American (AMR) AF: 0.725 AC: 25051 AN: 34572

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 9396 AN: 19436

East Asian (EAS) AF: 0.766 AC: 26716 AN: 34880

South Asian (SAS) AF: 0.721 AC: 47044 AN: 65238

European-Finnish (FIN) AF: 0.467 AC: 17720 AN: 37928

Middle Eastern (MID) AF: 0.586 AC: 1515 AN: 2586

European-Non Finnish (NFE) AF: 0.434 AC: 180557 AN: 415756

Other (OTH) AF: 0.516 AC: 17430 AN: 33762

GnomAD4 genome AF: 0.581 AC: 88213 AN: 151784 Hom.: 27866 Cov.: 30 AF XY: 0.587 AC XY: 43498 AN XY: 74152

African (AFR) AF: 0.805 AC: 33322 AN: 41414

American (AMR) AF: 0.644 AC: 9818 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3466

East Asian (EAS) AF: 0.760 AC: 3888 AN: 5118

South Asian (SAS) AF: 0.728 AC: 3499 AN: 4804

European-Finnish (FIN) AF: 0.463 AC: 4872 AN: 10518

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

European-Non Finnish (NFE) AF: 0.430 AC: 29222 AN: 67916

Other (OTH) AF: 0.571 AC: 1204 AN: 2108

Alfa AF: 0.527 Hom.: 2944

Bravo AF: 0.604

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.40
PhyloP100		-0.71
Mutation Taster		=100/0	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: rs4818868; hg19: chr21-45222058; COSMIC: COSV68544810; COSMIC: COSV68544810;