rs2276246

Variant names:

• chr21-43791051-G-A
• rs2276246
• NM_003683.6:c.134-299G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003683.6(RRP1):​c.134-299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 511,324 control chromosomes in the GnomAD database, including 14,177 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 0.18 (3258 hom., cov: 33)
  • Exomes 𝑓: 0.23 (10919 hom.)
• Consequence: RRP1 NM_003683.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRP1	NM_003683.6	c.134-299G>A		intron_variant	Intron 1 of 12	ENST00000497547.2	NP_003674.1
RRP1	XM_017028485.3	c.134-299G>A		intron_variant	Intron 1 of 12		XP_016883974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP1	ENST00000497547.2	c.134-299G>A		intron_variant	Intron 1 of 12	1	NM_003683.6	ENSP00000417464.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27957 AN: 152122 Hom.: 3248 Cov.: 33

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.261 AC: 33584 AN: 128622 Hom.: 5129 AF XY: 0.256 AC XY: 18012 AN XY: 70386

Gnomad AFR exome AF: 0.0667

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.465

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.232 AC: 83143 AN: 359084 Hom.: 10919 Cov.: 0 AF XY: 0.234 AC XY: 46980 AN XY: 201080

Gnomad4 AFR exome AF: 0.0666

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.184 AC: 27977 AN: 152240 Hom.: 3258 Cov.: 33 AF XY: 0.192 AC XY: 14274 AN XY: 74428

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.198

Alfa AF: 0.192 Hom.: 1587

Bravo AF: 0.182

Asia WGS AF: 0.347 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2276246; hg19: chr21-45210932; COSMIC: COSV71856937; COSMIC: COSV71856937;