21-43802177-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003683.6(RRP1):​c.1010-97A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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>T		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>T		intron	N/A	ENSP00000417464.1
	RRP1	ENST00000467112.5	TSL:1	n.1124-97A>T		intron	N/A
	RRP1	ENST00000471909.1	TSL:1	n.649-97A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 663422 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 352674

African (AFR) AF: 0.00 AC: 0 AN: 18190

American (AMR) AF: 0.00 AC: 0 AN: 34612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19474

East Asian (EAS) AF: 0.00 AC: 0 AN: 34914

South Asian (SAS) AF: 0.00 AC: 0 AN: 65290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 416544

Other (OTH) AF: 0.00 AC: 0 AN: 33822

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.049
DANN	Benign	0.59
PhyloP100		-0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;