Genetic Variant NM_003683.6:c.134-299G>A (chr21-43791051-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.241

Publications

12 publications found

Variant links:

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]

RRP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.134-299G>A		intron	N/A	NP_003674.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RRP1	ENST00000497547.2	TSL:1 MANE Select	c.134-299G>A	intron	N/A	ENSP00000417464.1
RRP1	ENST00000473988.1	TSL:3	n.559G>A	non_coding_transcript_exon	Exon 1 of 2
RRP1	ENST00000483896.5	TSL:3	n.*31G>A	non_coding_transcript_exon	Exon 2 of 9	ENSP00000426898.1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27957

AN:

152122

Hom.:

3248

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.261

AC:

33584

AN:

128622

AF XY:

0.256

show subpopulations

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 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.:

AF XY:

0.234

AC XY:

46980

AN XY:

201080

show subpopulations

African (AFR)

AF:

0.0666

AC:

711

AN:

10676

American (AMR)

AF:

0.359

AC:

10312

AN:

28704

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

2691

AN:

13486

East Asian (EAS)

AF:

0.460

AC:

6427

AN:

13984

South Asian (SAS)

AF:

0.283

AC:

17017

AN:

60184

European-Finnish (FIN)

AF:

0.273

AC:

4204

AN:

15398

Middle Eastern (MID)

AF:

0.181

AC:

560

AN:

3086

European-Non Finnish (NFE)

AF:

0.191

AC:

37396

AN:

195360

Other (OTH)

AF:

0.210

AC:

3825

AN:

18206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

3129

6258

9387

12516

15645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.184

AC:

27977

AN:

152240

Hom.:

3258

Cov.:

AF XY:

0.192

AC XY:

14274

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0641

AC:

2663

AN:

41564

American (AMR)

AF:

0.283

AC:

4323

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

657

AN:

3472

East Asian (EAS)

AF:

0.470

AC:

2437

AN:

5180

South Asian (SAS)

AF:

0.292

AC:

1406

AN:

4820

European-Finnish (FIN)

AF:

0.282

AC:

2986

AN:

10584

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.187

AC:

12697

AN:

68012

Other (OTH)

AF:

0.198

AC:

418

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1145

2290

3434

4579

5724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.191

Hom.:

1727

Bravo

AF:

0.182

Asia WGS

AF:

0.347

AC:

1208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.9

(source)

DANN

Benign

0.57

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over