21-43804116-A-G

Variant names:

• chr21-43804116-A-G
• rs762408
• ENST00000467112.5:n.1842A>G

Variant summary

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

The ENST00000467112.5(RRP1):​n.1842A>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 0.543 in 281,826 control chromosomes in the GnomAD database, including 45,286 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 (27849 hom., cov: 34)
  • Exomes 𝑓: 0.50 (17437 hom.)
• Consequence: RRP1 ENST00000467112.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000467112.5. 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.*342A>G		3_prime_UTR	Exon 13 of 13	NP_003674.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1	ENST00000467112.5	TSL:1	n.1842A>G		non_coding_transcript_exon	Exon 10 of 10
	RRP1	ENST00000471909.1	TSL:1	n.1367A>G		non_coding_transcript_exon	Exon 8 of 8
	RRP1	ENST00000497547.2	TSL:1 MANE Select	c.*342A>G		3_prime_UTR	Exon 13 of 13	ENSP00000417464.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88194 AN: 152114 Hom.: 27800 Cov.: 34

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.499 AC: 64609 AN: 129592 Hom.: 17437 Cov.: 0 AF XY: 0.504 AC XY: 32981 AN XY: 65388

African (AFR) AF: 0.795 AC: 3291 AN: 4142

American (AMR) AF: 0.673 AC: 2622 AN: 3896

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 2341 AN: 4854

East Asian (EAS) AF: 0.778 AC: 7360 AN: 9456

South Asian (SAS) AF: 0.712 AC: 5025 AN: 7062

European-Finnish (FIN) AF: 0.453 AC: 3598 AN: 7938

Middle Eastern (MID) AF: 0.567 AC: 371 AN: 654

European-Non Finnish (NFE) AF: 0.430 AC: 35600 AN: 82860

Other (OTH) AF: 0.504 AC: 4401 AN: 8730

GnomAD4 genome AF: 0.580 AC: 88298 AN: 152234 Hom.: 27849 Cov.: 34 AF XY: 0.585 AC XY: 43566 AN XY: 74422

African (AFR) AF: 0.802 AC: 33329 AN: 41550

American (AMR) AF: 0.643 AC: 9851 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3472

East Asian (EAS) AF: 0.760 AC: 3930 AN: 5172

South Asian (SAS) AF: 0.727 AC: 3508 AN: 4826

European-Finnish (FIN) AF: 0.464 AC: 4908 AN: 10586

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

European-Non Finnish (NFE) AF: 0.429 AC: 29183 AN: 67994

Other (OTH) AF: 0.569 AC: 1203 AN: 2114

Alfa AF: 0.491 Hom.: 53381

Bravo AF: 0.603

Asia WGS AF: 0.751 AC: 2610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.18
PhyloP100		-0.50
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: rs762408; hg19: chr21-45223997;