Variant 5-97163231-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_018343.3(RIOK2):c.1495-6T>C variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00244 in 1,611,782 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

RIOK2
NM_018343.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006099

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 5-97163231-A-G is Benign according to our data. Variant chr5-97163231-A-G is described in ClinVar as [Benign]. Clinvar id is 768023.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1896/152326) while in subpopulation AFR AF= 0.0423 (1758/41562). AF 95% confidence interval is 0.0407. There are 38 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RIOK2	NM_018343.3 linkuse as main transcript	c.1495-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000283109.8
RIOK2	XM_017009628.2 linkuse as main transcript	c.934-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
LIX1-AS1	XR_007058883.1 linkuse as main transcript	n.4605-19777A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RIOK2	ENST00000283109.8 linkuse as main transcript	c.1495-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_018343.3	P1	Q9BVS4-1
LIX1-AS1	ENST00000504578.2 linkuse as main transcript	n.574-19777A>G	intron_variant, non_coding_transcript_variant	5
RIOK2	ENST00000511293.1 linkuse as main transcript	c.314-6T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1886

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.00330

AC:

819

AN:

247864

Hom.:

AF XY:

0.00235

AC XY:

316

AN XY:

134226

show subpopulations

Gnomad AFR exome

AF:

0.0439

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00139

AC:

2035

AN:

1459456

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

878

AN XY:

726146

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.00260

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.000157

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.0124

AC:

1896

AN:

152326

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

928

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00559

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000061

dbscSNV1_RF

Benign

0.024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over