Genetic Variant RIOK2:c.498+137T>C (chr5-97176979-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018343.3(RIOK2):c.498+137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 712,506 control chromosomes in the GnomAD database, including 162,216 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 0.68 ( 35241 hom., cov: 32)

Exomes 𝑓: 0.67 ( 126975 hom. )

Consequence

RIOK2
NM_018343.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.601

Publications

8 publications found

Variant links:

Genes affected

RIOK2 (HGNC:18999): (RIO kinase 2) Predicted to enable protein kinase activity. Involved in several processes, including positive regulation of rRNA processing; positive regulation of ribosomal small subunit export from nucleus; and regulation of mitotic metaphase/anaphase transition. Located in cytoplasm. Part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

RIOK2 links:

LIX1-AS1 (HGNC:52976): (LIX1 and RIOK2 antisense RNA 1)

LIX1-AS1 links:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018343.3. 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
	RIOK2	NM_018343.3	MANE Select	c.498+137T>C		intron	N/A	NP_060813.2	Q9BVS4-1
	RIOK2	NM_001159749.2		c.498+137T>C		intron	N/A	NP_001153221.1	Q9BVS4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIOK2	ENST00000283109.8	TSL:1 MANE Select	c.498+137T>C	intron	N/A	ENSP00000283109.3	Q9BVS4-1
RIOK2	ENST00000508447.1	TSL:1	c.498+137T>C	intron	N/A	ENSP00000420932.1	Q9BVS4-2
RIOK2	ENST00000924329.1		c.498+137T>C	intron	N/A	ENSP00000594388.1

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

103212

AN:

151938

Hom.:

35190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.741

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.658

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.638

GnomAD4 exome

AF:

0.672

AC:

376397

AN:

560450

Hom.:

126975

Cov.:

AF XY:

0.674

AC XY:

202937

AN XY:

301074

show subpopulations

African (AFR)

AF:

0.673

AC:

9378

AN:

13926

American (AMR)

AF:

0.600

AC:

12970

AN:

21624

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

11050

AN:

16716

East Asian (EAS)

AF:

0.636

AC:

20823

AN:

32728

South Asian (SAS)

AF:

0.696

AC:

36782

AN:

52820

European-Finnish (FIN)

AF:

0.753

AC:

25236

AN:

33506

Middle Eastern (MID)

AF:

0.597

AC:

1303

AN:

2184

European-Non Finnish (NFE)

AF:

0.669

AC:

239020

AN:

357368

Other (OTH)

AF:

0.671

AC:

19835

AN:

29578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

5465

10931

16396

21862

27327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2304

4608

6912

9216

11520

<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:

0.680

AC:

103328

AN:

152056

Hom.:

35241

Cov.:

AF XY:

0.683

AC XY:

50765

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.680

AC:

28176

AN:

41458

American (AMR)

AF:

0.639

AC:

9759

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.658

AC:

2283

AN:

3470

East Asian (EAS)

AF:

0.651

AC:

3362

AN:

5162

South Asian (SAS)

AF:

0.694

AC:

3346

AN:

4818

European-Finnish (FIN)

AF:

0.756

AC:

8002

AN:

10584

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.680

AC:

46211

AN:

67962

Other (OTH)

AF:

0.639

AC:

1350

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1670

3340

5011

6681

8351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.674

Hom.:

149817

Bravo

AF:

0.666

Asia WGS

AF:

0.673

AC:

2339

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.2

(source)

DANN

Benign

0.38

PhyloP100

0.60

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

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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