rs762408

chr21-43804116-A-Gchr21-43804116-A-Tchr21-43804116-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.*342A>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 0.543 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 NM_003683.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRP1	NM_003683.6	c.*342A>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.*342A>G		3_prime_UTR_variant	13/13	1	NM_003683.6	P1
RRP1	ENST00000467112.5	n.1842A>G		non_coding_transcript_exon_variant	10/10	1
RRP1	ENST00000471909.1	n.1367A>G		non_coding_transcript_exon_variant	8/8	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

Gnomad4 AFR exome AF: 0.795

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.778

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.504

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

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.569

Alfa AF: 0.461 Hom.: 27399

Bravo AF: 0.603

Asia WGS AF: 0.751 AC: 2610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.37
Dann	Benign	0.18

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: rs762408; hg19: chr21-45223997;