Genetic Variant RRP9:c.88-70G>A (chr3-51941561-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004704.5(RRP9):c.88-70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,387,700 control chromosomes in the GnomAD database, including 40,614 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 0.28 ( 6662 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33952 hom. )

Consequence

RRP9
NM_004704.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.418

Publications

8 publications found

Variant links:

Genes affected

RRP9 (HGNC:16829): (ribosomal RNA processing 9, U3 small nucleolar RNA binding protein) This gene encodes a member of the WD-repeat protein family. The encoded protein is a component of the nucleolar small nuclear ribonucleoprotein particle (snoRNP) and is essential for 18s rRNA processing during ribosome synthesis. It contains seven WD domains required for nucleolar localization and specific interaction with the U3 small nucleolar RNA (U3 snoRNA). [provided by RefSeq, Oct 2012]

RRP9 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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004704.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP9	NM_004704.5	MANE Select	c.88-70G>A		intron	N/A	NP_004695.1	O43818

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RRP9	ENST00000232888.7	TSL:1 MANE Select	c.88-70G>A	intron	N/A	ENSP00000232888.6	O43818
RRP9	ENST00000897235.1		c.88-70G>A	intron	N/A	ENSP00000567294.1
RRP9	ENST00000940586.1		c.88-70G>A	intron	N/A	ENSP00000610645.1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42154

AN:

151850

Hom.:

6653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.213

AC:

263587

AN:

1235736

Hom.:

33952

Cov.:

AF XY:

0.210

AC XY:

130906

AN XY:

623644

show subpopulations

African (AFR)

AF:

0.405

AC:

11468

AN:

28330

American (AMR)

AF:

0.517

AC:

22283

AN:

43100

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

6500

AN:

24252

East Asian (EAS)

AF:

0.451

AC:

17322

AN:

38376

South Asian (SAS)

AF:

0.154

AC:

12508

AN:

81366

European-Finnish (FIN)

AF:

0.173

AC:

8998

AN:

52098

Middle Eastern (MID)

AF:

0.242

AC:

1269

AN:

5236

European-Non Finnish (NFE)

AF:

0.188

AC:

171475

AN:

910416

Other (OTH)

AF:

0.224

AC:

11764

AN:

52562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

10420

20841

31261

41682

52102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5742

11484

17226

22968

28710

<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:

0.278

AC:

42192

AN:

151964

Hom.:

6662

Cov.:

AF XY:

0.278

AC XY:

20683

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.391

AC:

16165

AN:

41300

American (AMR)

AF:

0.402

AC:

6138

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

914

AN:

3470

East Asian (EAS)

AF:

0.407

AC:

2106

AN:

5180

South Asian (SAS)

AF:

0.162

AC:

783

AN:

4824

European-Finnish (FIN)

AF:

0.169

AC:

1785

AN:

10588

Middle Eastern (MID)

AF:

0.281

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.198

AC:

13496

AN:

68002

Other (OTH)

AF:

0.288

AC:

609

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

1503

3007

4510

6014

7517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.226

Hom.:

6962

Bravo

AF:

0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.1

(source)

DANN

Benign

0.87

PhyloP100

-0.42

PromoterAI

-0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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