NM_018343.3:c.1495-6T>C

Variant names:

• chr5-97163231-A-G
• rs56023991
• NM_018343.3:c.1495-6T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_018343.3(RIOK2):​c.1495-6T>C variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00006099
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.18
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.1495-6T>C		splice_region_variant, intron_variant	Intron 9 of 9	ENST00000283109.8	NP_060813.2
RIOK2	XM_017009628.2	c.934-6T>C		splice_region_variant, intron_variant	Intron 7 of 7		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8	c.1495-6T>C		splice_region_variant, intron_variant	Intron 9 of 9	1	NM_018343.3	ENSP00000283109.3
RIOK2	ENST00000511293.1	c.313-6T>C		splice_region_variant, intron_variant	Intron 3 of 3	3		ENSP00000421830.1
LIX1-AS1	ENST00000504578.2	n.574-19777A>G		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1886 AN: 152208 Hom.: 38 Cov.: 32

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

GnomAD2 exomes AF: 0.00330 AC: 819 AN: 247864 AF XY: 0.00235

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 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.: 36 Cov.: 31 AF XY: 0.00121 AC XY: 878 AN XY: 726146

African (AFR) AF: 0.0457 AC: 1523 AN: 33332

American (AMR) AF: 0.00260 AC: 116 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86102

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52812

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5760

European-Non Finnish (NFE) AF: 0.000157 AC: 174 AN: 1110824

Other (OTH) AF: 0.00313 AC: 189 AN: 60320

GnomAD4 genome AF: 0.0124 AC: 1896 AN: 152326 Hom.: 38 Cov.: 32 AF XY: 0.0125 AC XY: 928 AN XY: 74480

African (AFR) AF: 0.0423 AC: 1758 AN: 41562

American (AMR) AF: 0.00621 AC: 95 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68030

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00559 Hom.: 12

Bravo AF: 0.0151

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		5.2
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs56023991; hg19: chr5-96498935;